Epilepsy
Epilepsy is a group of
non-communicable neurological disorders characterized by recurrent epileptic
seizures. Epileptic seizures can vary from brief and
nearly undetectable periods to long periods of vigorous shaking due to abnormal
electrical activity in the brain. These
episodes can result in physical injuries, either directly from broken bones,
accidents or otherwise. In epilepsy,
seizures tend to recur and may 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 the alarming nature of their symptoms.
The underlying mechanism of
epileptic seizures is excessive and abnormal neuronal activity in the cortex of
the brain which can be observed in the electroencephalogram (EEG) of an
individual. The reason this occurs in most cases of epilepsy is unknown
(idiopathic); some cases occur as the result of brain injury, stroke, brain
tumors, infections of the brain, or birth defects through a process known as palatogenesis.
Known genetic mutations are linked to a
small proportion of cases. 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 EEG,
but a normal test does not rule out the condition.
Epilepsy that occurs because
of other issues may be preventable. Seizures are controllable with medication
in about 69% of cases; inexpensive anti-seizure medications 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 2020, about 50 million
people have epilepsy worldwide. Nearly
80% of cases occur in the developing world. In 2015, it resulted in 125,000 deaths, an
increase from 112,000 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, with the chance of experiencing a second seizure
rising to 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.
Epilepsy is characterized by
a long-term risk of recurrent epileptic seizures. These seizures may present in several ways
depending on the parts of the brain involved and the person's age.
Seizures
The most common type (60%)
of seizures is convulsive which involve involuntary muscle contractions. Of these, one-third begin as generalized
seizures from the start, affecting both hemispheres of the brain and impairing
consciousness. Two-thirds begin as focal
seizures (which affect one hemisphere of the brain) which may 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
Certain experiences, known
as auras, often precede focal seizures. The seizures can include sensory (visual,
hearing, or smell), psychic, autonomic, and motor phenomena depending on which
part of the brain is involved. Muscle
jerks 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, which are
non-consciously generated activities and mostly simple repetitive movements
like smacking the lips or more complex activities such as attempts to pick up something.
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 occur
with a contraction of the limbs followed by their extension and arching of the
back which lasts 10–30 seconds (the tonic phase). A cry may be heard due to
contraction of the chest muscles, 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.
People experiencing a seizure may
bite their tongue, either the tip or on the sides; 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
very brief spasms of muscles in either a few areas or all over. These sometimes cause the person to fall,
which can cause injury. Absence seizures
can be subtle with only a slight turn of the head or eye blinking with impaired
consciousness; typically, the person does not fall over and returns to normal
right after it ends. Atonic seizures
involve losing muscle activity for greater than one second, typically occurring
on both sides of the body. Rarer seizure
types can cause involuntary unnatural laughter (gelastic), crying (dyscrastic),
or more complex experiences such as déjà vu.
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 only when sleeping.
Seizure clusters
Patients with epilepsy may
experience seizure clusters which may be broadly defined as an acute
deterioration in seizure control. The prevalence of seizure clusters is
uncertain given that studies have used different definitions to define them. However, estimates suggest that the
prevalence may range from 5% to 50% of epilepsy patients. Refractory epilepsy patients who have a high
seizure frequency are at the greatest risk for having seizure clusters. Seizure clusters are associated with increased
healthcare utilization, worse quality of life, impaired psychosocial
functioning, and increased mortality. Benzodiazepines are used as an acute treatment
for seizure clusters.
Posticta
After the active portion of
a seizure (the ictal state) there is typically a period of recovery during
which there is confusion, referred to as the postictal period, before a normal
level of consciousness returns. It
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 focal seizure. It typically
lasts for seconds to minutes but may rarely last for a day or two.
Psychosoci
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 disabilities 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 disorder.
Certain disorders occur more
often in people with epilepsy, depending partly on the epilepsy syndrome
present. These include depression, anxiety, obsessive–compulsive disorder
(OCD), and migraine. Attention deficit hyperactivity disorder
(ADHD) affects three to five times more children with epilepsy than children
without the condition. ADHD and epilepsy have significant consequences on a
child's behavioral, learning, and social development. Epilepsy is also more common in children with
autism.
Approximately one-in-three
people with epilepsy have a lifetime history of a psychiatric disorder. There
are believed to be multiple causes for this including pathophysiological
changes related to the epilepsy itself as well as adverse experiences related
to living with epilepsy (e.g., stigma, discrimination). In addition, it is thought that the
relationship between epilepsy and psychiatric disorders is not unilateral but
rather bidirectional. For example, patients with depression have an increased
risk for developing new-onset epilepsy.
The presence of comorbid
depression or anxiety in patients with epilepsy is associated with a poorer
quality of life, increased mortality, increased healthcare utilization and a
worse response to treatment (including surgical). Anxiety disorders and depression may explain
more variability in quality of life than seizure type or frequency. There is evidence that both depression and
anxiety disorders are underdiagnosed and undertreated in patients with
epilepsy.
Causes
Epilepsy can have both
genetic and acquired causes, with the interaction of these factors in many
cases. Established acquired causes include serious
brain trauma, stroke, tumors, and brain problems resulting from 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.[64] 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.
Phakomatoses
Phakomatoses, also known as
neurocutaneous disorders, are a group of multisystemic diseases that most
prominently affect the skin and central nervous system. They are caused by
defective development of the embryonic ectodermal tissue that is most often due
to a single genetic mutation. The brain, as well as other neural tissue and the
skin, are all derived from the ectoderm and thus defective development may
result in epilepsy as well as other manifestations such as autism and
intellectual disability. Some types of phakomatoses such as tuberous sclerosis
complex and Sturge-Weber syndrome have a higher prevalence of epilepsy relative
to others such as neurofibromatosis type 1.
Tuberous sclerosis complex
is an autosomal dominant disorder that is caused by mutations in either the
TSC1 or TSC2 gene and it affects approximately 1 in 6,000-10,000 live births. These
mutations result in the upregulation of the mechanistic target of rapamycin
(mTOR) pathway which leads to the growth of tumors in many organs including the
brain, skin, heart, eyes, and kidneys. In addition, abnormal mTOR activity is
believed to alter neural excitability. The prevalence of epilepsy is estimated to be
80-90%. The majority of cases of
epilepsy present within the first 3 years of life and are medically refractory. Relatively recent developments for the
treatment of epilepsy in TSC patients include mTOR inhibitors, cannabidiol and
vigabatrin. Epilepsy surgery is often pursued.
Sturge-Weber syndrome is
caused by an activating somatic mutation in the GNAQ gene, and it affects approximately
1 in 20,000-50,000 live births. The
mutation results in vascular malformations affecting the brain, skin, and eyes.
The typical presentation includes a facial port-wine birthmark, ocular angiomas
and cerebral vascular malformations which are most often unilateral but are
bilateral in 15% of cases. The
prevalence of epilepsy is 75-100%, and
higher in those with bilateral involvement. Seizures typically occur within the first two
years of life and are refractory in nearly half of cases. However, high rates of seizure freedom with
surgery have been reported in as many as 83%.
Neurofibromatosis type 1 is the most common phakomatoses and occurs in approximately 1 in 3,000 live births. It is caused by autosomal dominant mutations in the Neurofibromin 1 gene. Clinical manifestations are variable but may include hyperpigmented skin marks, hamartomas of the iris called Lisch nodules, neurofibromas, optic pathway gliomas and cognitive impairment. The prevalence of epilepsy is estimated to be 4-7%.[ seizures are typically easier to control with anti-seizure medications relative to other phakomatoses but in some refractory cases surgery may need to be pursued.
Acquired
Epilepsy may occur as a
result of several 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, 6–10% develop
epilepsy. Risk factors for post-stroke epilepsy include
stroke severity, cortical involvement, hemorrhage and early seizures. 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 that includes celiac disease,
epilepsy, and calcifications in the brain. A 2012 review estimates that between 1% and 6%
of people with epilepsy have celiac disease while 1% of the general population
has the condition.
The risk of epilepsy
following meningitis is less than 10%; it 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 2.5-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.
Mechanism
Normally brain electrical
activity is non-synchronous, as large numbers of neurons do not normally fire
at the same time, but rather fire in order as signals travel throughout the
brain. Neuron activity is regulated by numerous
factors both within the cell and the cellular environment. Factors within the
neuron include the type, number and distribution of ion channels, changes to
receptors and changes of gene expression.
Factors around the neuron include ion concentrations, synaptic plasticity,
and regulation of transmitter breakdown by glial cells.
Epilepsy
The exact mechanism for
epilepsy is unknown but a little is known about its cellular and network
mechanisms. However, it is unknown under which circumstances the brain shifts
into the activity of a seizure with its excessive synchronization. Changes in MicroRNAs (miRNAs) levels seems to
play a leading role. MicroRNAs (miRNAs) are a family of small non-coding RNAs
that control the expression levels of multiple proteins by decreasing mRNA
stability and translation, and could therefore be key regulatory mechanisms and
therapeutic targets in epilepsy
In epilepsy, the resistance
of excitatory neurons to fire during this period is decreased. This may occur
due to changes in ion channels or inhibitory neurons not functioning properly. This then results in a specific area from
which seizures may develop, known as a "seizure focus". Another
mechanism of epilepsy may be the up-regulation of excitatory circuits or
down-regulation of inhibitory circuits following an injury to the brain.] These
secondary epilepsies occur through processes known as epileptogenic. Failure of the blood–brain barrier may also be
a causal mechanism as it would allow substances in the blood to enter the brain.
Seizures
There is evidence that
epileptic seizures are usually not a random event. Seizures are often brought
on by factors (also known as triggers) such as stress, excessive alcohol use,
flickering light, or a lack of sleep, among others. The term seizure threshold
is used to indicate the amount of stimulus necessary to bring about a seizure;
this threshold is lowered in epilepsy.
In epileptic seizures a
group of neurons begin firing in an abnormal, excessive, and synchronized
manner. This results in a wave of depolarization known as a paroxysmal
depolarizing shift. Normally, after an
excitatory neuron fires it becomes more resistant to firing for a period of
time This is due in part to the effect of inhibitory neurons, electrical
changes within the excitatory neuron, and the negative effects of adenosine.
Focal seizures begin in one
area of the brain while generalized seizures begin in both hemispheres. Some
types of seizures may change brain structure, while others appear to have
little effect. Gliosis, neuronal loss,
and atrophy of specific areas of the brain are linked to epilepsy but it is
unclear if epilepsy causes these changes or if these changes result in
epilepsy.
The seizures can be
described on different scales, from the cellular level to the whole brain.
These are several concomitant factors, which on different scale can
"drive" the brain to pathological states and trigger a seizure.
Diagnosis
An EEG can aid in locating
the focus of the epileptic seizure.
The diagnosis of epilepsy is
typically made based on observation of the seizure onset and the underlying
cause. An electroencephalogram (EEG) to
look for abnormal patterns of brain waves and neuroimaging (CT scan or MRI) to
look at the structure of the brain are also usually part of the initial
investigations. 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.
Epilepsy is a disorder of
the brain defined by any of the following conditions:
At least two unprovoked (or
reflex) seizures occurring more than 24 hours apart
One unprovoked (or reflex)
seizure and a probability of further seizures similar to the general recurrence
risk (at least 60%) after two unprovoked seizures, occurring over the next 10
years
Diagnosis of an epilepsy
syndrome
Furthermore, epilepsy is
considered to be resolved for individuals who had an age-dependent epilepsy
syndrome but are now past that age or those who have remained seizure-free for
the last 10 years, with no seizure medicines for the last 5 years.
This 2014 definition of the
International League Against Epilepsy is a clarification of the ILAE 2005
conceptual definition, according to which epilepsy is "a disorder of the
brain characterized by an enduring predisposition to generate epileptic
seizures and by the neurobiologic, cognitive, psychological, and social
consequences of this condition. The definition of epilepsy requires the
occurrence of at least one epileptic seizure."
It is, therefore, possible
to outgrow epilepsy or to undergo treatment that causes epilepsy to be
resolved, but with no guarantee that it will not return. In the definition,
epilepsy is now called a disease, rather than a disorder. This was a decision
of the executive committee of the ILAE, taken because the word
"disorder," while perhaps having less stigma than does
"disease," also does not express the degree of seriousness that
epilepsy deserves.
The definition is practical
in nature and is designed for clinical use. In particular, it aims to clarify
when an "enduring predisposition" according to the 2005 conceptual
definition is present. Researchers, statistically minded epidemiologists, and
other specialized groups may choose to use the older definition or a definition
of their own devising. The ILAE considers doing so is perfectly allowable, so
long as it is clear what definition is being used.
Classification
Revised operational scheme
of seizure classification, ILAE, 2017
In contrast to the
classification of seizures which focuses on what happens during a seizure, the
classification of epilepsies focuses on the underlyings causes. When a person
is admitted to hospital after an epileptic seizure the diagnostic workup
results preferably in the seizure itself being classified (e.g. tonic-clonic)
and in the underlying disease being identified (e.g. hippocampal sclerosis .The
name of the diagnosis finally made depends on the available diagnostic results
and the applied definitions and classifications (of seizures and epilepsies)
and its respective terminology.
The International League
Against Epilepsy (ILAE) provided a classification of the epilepsies and
epileptic syndromes in 1989 as follows:
Unknown cause (e.g. benign
childhood epilepsy with centrotemporal spikes)
Symptomatic/cryptogenic
(e.g. temporal lobe epilepsy)
Generalized
Unknown cause (e.g.
childhood absence epilepsy)
Cryptogenic or symptomatic
(e.g. Lennox-Gastaut syndrome)
Symptomatic (e.g. early
infantile epileptic encephalopathy with burst suppression)
Epilepsies and syndromes
undetermined whether focal or generalized
With both generalized and
focal seizures (e.g. epilepsy with continuous spike-waves during slow wave
sleep)
Special syndromes (with
situation-related seizures)
This classification was
widely accepted but has also been criticized mainly because the underlying
causes of epilepsy (which are a major determinant of clinical course and
prognosis) were not covered in detail. In 2010 the ILAE Commission for Classification
of the Epilepsies addressed this issue and divided epilepsies into three
categories (genetic, structural/metabolic, unknown cause that were refined in
their 2011 recommendation into four categories and a number of subcategories
reflecting recent technologic and scientific advances.
Unknown cause (mostly
genetic or presumed genetic origin)
Pure epilepsies due to
single gene disorders
Pure epilepsies with complex
inheritance
Symptomatic (associated with
gross anatomic or pathologic abnormalities)
Mostly genetic or
developmental causation
Childhood epilepsy syndromes
Progressive myoclonic
epilepsies
Neurocutaneous syndromes
Other neurologic single gene
disorders
Disorders of chromosome
function
Developmental anomalies of
cerebral structure
Mostly acquired causes
Hippocampal sclerosis
Perinatal and infantile
causes
Cerebral trauma, tumor or
infection
Cerebrovascular disorders
Cerebral immunologic
disorders
Degenerative and other
neurologic conditions
Provoked (a specific
systemic or environmental factor is the predominant cause of the seizures)
Provoking factors
Reflex epilepsies
Cryptogenic (presumed
symptomatic nature in which the cause has not been identified)
A revised, operational classification
of seizure types has been introduced by the ILAE. It allows more clearly understood terms and
clearly defines focal and generalized onset dichotomy, when possible, even
without observing the seizures based on description by patient or observers. The essential changes in terminology are that
"partial" is called "focal" with awareness used as a
classifier for focal seizures -based on description focal seizures are now
defined as behavioral arrest, automatisms, cognitive, autonomic, emotional or
hyperkinetic variants while atonic, myoclonic, clonic, infantile spasms, and
tonic seizures may be either focal or generalized based on their onset. Several
terms that were not clear or consistent in description were removed such as
dyscognitive, psychic, simple and complex partial, while "secondarily
generalized" is replaced by a clearer term "focal to bilateral tonic
clonic seizure". New seizure types now believed to be generalized are
eyelid myoclonia, myoclonic atonic, myoclonic absence, and myoclonic tonic
clonic. Sometimes it is possible to classify seizures as focal or generalized
based on presenting features even though onset in not known. This system is
based on the 1981 seizure classification modified in 2010 and principally is
the same with an effort to improve the flexibility and clarity of use to
understand seizures types better in keeping with current knowledge.
Syndromes
Cases of epilepsy may be
organized into epilepsy syndromes by the specific features that are present.
These features include the age that seizure begin, the seizure types, EEG
findings, among others. Identifying an epilepsy syndrome is useful as it helps
determine the underlying causes as well as what anti-seizure medication should
be tried.
The ability to categorize a
case of epilepsy into a specific syndrome occurs more often with children since
the onset of seizures is commonly early. Less serious examples are benign rolandic
epilepsy (2.8 per 100,000), childhood absence epilepsy (0.8 per 100,000) and
juvenile myoclonic epilepsy (0.7 per 100,000).
Severe syndromes with diffuse
brain dysfunction caused, at least partly, by some aspect of epilepsy, are also
referred to as developmental and epileptic encephalopathies. These are
associated with frequent seizures that are resistant to treatment and cognitive
dysfunction, for instance Lennox–Gastaut syndrome (1-2% of all persons with
epilepsy. Dravet syndrome(1: 15000-40000
worldwide, and West syndrome(1-9: 100000 Genetics is believed to play an
important role in epilepsies by a number of mechanisms. Simple and complex
modes of inheritance have been identified for some of them. However, extensive
screening have failed to identify many single gene variants of large effect.
More recent exome and genome sequencing studies have begun to reveal a number
of de novo gene mutations that are responsible for some epileptic
encephalopathies, including CHD2 and SYNGAP1 and DNM1, GABBR2, FASN and RYR
Syndromes in which causes
are not clearly identified are difficult to match with categories of the
current classification of epilepsy. Categorization for these cases was made
somewhat arbitrarily. The idiopathic (unknown cause) category of the 2011
classification includes syndromes in which the general clinical features and/or
age specificity strongly point to a presumed genetic cause. Some childhood epilepsy syndromes are included
in the unknown cause category in which the cause is presumed genetic, for
instance benign rolandic epilepsy. Others are included in symptomatic despite a
presumed genetic cause (in at least in some cases), for instance Lennox-Gastaut
syndrome. Clinical syndromes in which
epilepsy is not the main feature (e.g. Angelman syndrome) were categorized
symptomatic but it was argued to include these within the category idiopathic. Classification of epilepsies and particularly
of epilepsy syndromes will change with advances in research.
Tests
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.[120] In children it is typically only needed after a second seizure
unless specified by a specialist. 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 comes to 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. Together with EEG and neuroimaging, genetic
testing is becoming one of the most important diagnostic technique for
epilepsy, as a diagnosis might be achieved in a relevant proportion of cases
with severe epilepsies, both in children and adults. For
those with negative genetic testing, in some it might be important to repeat or
re-analyze previous genetic studies after 2–3 year
A high blood prolactin level
within the first 20 minutes following a seizure may be useful to help confirm
an epileptic seizure as opposed to psychogenic non-epileptic seizure. Serum
prolactin level is less useful for detecting focal seizure, 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 an epilepsy syndrome.
Attacks of the movement disorder paroxysmal dyskinesia may be taken for
epileptic seizures. The cause of a drop attack can be, among many things, an
atonic seizure.
Children may have behaviors
that are easily mistaken for epileptic seizures but are not. These include
breath-holding spells, bedwetting, night terrors, tics and shudder
attacks.[130] 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.
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.
Complication
Epilepsy can be dangerous
when seizure occurs at certain times. The possibility of drowning and having
car accident is higher. It is also dangerous when seizure occurs during
pregnancy. Certain anti-epileptic medications increase the risk of birth
defects. It is also found that people with epilepsy are more likely to have
psychological problems. Other complications include aspiration pneumonia and
difficulty learning.
Management
Wristbands or bracelets
denoting their condition are occasionally worn by epileptics should they need
medical assistance.
Epilepsy is usually treated
with daily medication once a second seizure has occurred, while medication may
be started after the first seizure in those at high risk for subsequent
seizures.[102] Supporting people's self-management of their condition may be
useful. In drug-resistant cases
different management options may be looked at including a special diet, the implantation
of a neurostimulator, or neurosurgery.
First aid
Rolling people with an
active tonic-clonic seizure onto their side and into the recovery position
helps prevent fluids from getting into the lungs. Putting fingers, a bite block or tongue depressor
in the mouth is not recommended as it might make the person vomit or result in
the rescuer being bitten. Efforts should
be taken to prevent further self-injury.[27] Spinal precautions are generally
not needed.
If a seizure lasts longer than 5 minutes or if there are more than two seizures in an hour without a return to a normal level of consciousness between them, it is considered a medical emergency known as status epilepticus. This may require medical help to keep the airway open and protected; a nasopharyngeal airway may be useful for this. At home the recommended initial medication for seizure of a long duration is midazolam placed in the mouth. Diazepam may also be used rectally.[141] In hospital, intravenous lorazepam is preferred. If two doses of benzodiazepines are not effective, other medications such as phenytoin are recommended. Convulsive status epilepticus that does not respond to initial treatment typically requires admission to the intensive care unit and treatment with stronger agents such asAnticonvulsants
The mainstay treatment of
epilepsy is anticonvulsant medications, possibly for the person's entire life. The choice of anticonvulsant is based on
seizure type, epilepsy syndrome, other medications used, other health problems,
and the person's age and lifestyle. A
single medication is recommended initially; if this is noeffective, switching
to a single other medication is recommended. Two medications at once is recommended only if
a single medication does not work. In
about half, the first agent is effective; a second single agent helps in about
13% and a third or two agents at the same time may help an additional 4%. About 30% of people continue to have seizures
despite anticonvulsant treatment.
There are a number of
medications available including phenytoin, carbamazepine and valproate.
Evidence suggests that these three phenytoin, carbamazepine, and valproate may
be equally effective in both focal and generalized seizures. Controlled release carbamazepine appears to
work as well as immediate release carbamazepine and may have fewer side
effects. Recently, Nux vomica and Cicuta
virosa have been shown to produce significant anti-epileptic effects and no
side effects. This could prove to be very helpful for a large segment of
population. In the United Kingdom, carbamazepine or lamotrigine are recommended
as first-line treatment for focal seizures, with levetiracetam and valproate as
second-line due to issues of cost and side effects. Valproate is recommended first-line for
generalized seizures with lamotrigine being second-line. In those with absence seizures, ethosuximide
or valproate are recommended; valproate is particularly effective in myoclonic
seizures and tonic or atonic seizures. If seizures are well-controlled on a
particular treatment, it is not usually necessary to routinely check the
medication levels in the blood.
The least expensive
anticonvulsant is phenobarbital at around US$5 a year. The World Health Organization gives it a
first-line recommendation in the developing world and it is commonly used
there. Access however may be difficult as some countries label it as a
controlled drug.
Adverse effects from
medications are reported in 10 to 90% of people, depending on how and from whom
the data is collected. Most adverse
effects are dose-related and mild. Some
examples include mood changes, sleepiness, or an unsteadiness in gait. Certain medications have side effects that are
not related to dose such as rashes, liver toxicity, or suppression of the bone
marrow. Up to a quarter of people stop
treatment due to adverse effects. Some
medications are associated with birth defects when used in pregnancy. Many of the common used medications, such as
valproate, phenytoin, carbamazepine, phenobarbital, and gabapentin have been
reported to cause increased risk of birth defects especially when used during
the first trimester. Despite this, treatment is often continued once effective,
because the risk of untreated epilepsy is believed to be greater than the risk
of the medications. Among the antiepileptic medicine and lamotrigine seem to
carry the lowest risk of causing birth defects.
Slowly stopping medications
may be reasonable in some people who do not have a seizure for two to four
years; however, around a third of people have a recurrence, most often during
the first six months. Stopping is
possible in about 70% of children and 60% of adults. Measuring medication
levels is not generally needed in those whose seizures are well controlled.
Surgery
Epilepsy surgery may be an
option for people with focal seizures that remain a problem despite other
treatments. These other treatments
include at least a trial of two or three medications. The goal of surgery is
total control of seizures and this may be achieved in 60–70% of cases. Common procedures include cutting out the hippocampus
via an anterior temporal lobe resection, removal of tumors, and removing parts
of the neocortex. Some procedures such
as a corpus callosotomy are attempted in an effort to decrease the number of
seizures rather than cure the condition. Following surgery, medications may be slowly
withdrawn in many cases.
Neurostimulation
Neurostimulation via
neuro-cybernetic prosthesis implantation, may be another option in those who
are not candidates for surgery, providing chronic, pulsatile electrical stimulation
of specific nerve or brain regions, alongside standard care. Three types have been used in those who do
not respond to medications: vagus nerve stimulation (VNS), anterior thalamic
stimulation, and closed-loop responsive stimulation.
Vagus nerve stimulation
Non-pharmacological
modulation of neurotransmitters via high-level VNS (h-VNS) may reduce seizure
frequency in children and adults who do not respond to medical and/or surgical
therapy, when compared with low-level VNS (l-VNS). In a 2022 Cochrane review of 4 randomized
controlled trials, with moderate certainty of evidence, people receiving h-VNS
treatment were 73% more likely (13% more likely to 164% more likely) to
experience a reduction in seizure frequency by at least 50% (the minimum threshold
defined for individual clinical response). Potentially 249 (163 to 380) per 1000 people
with drug-resistant epilepsy may achieve a 50% reduction in seizures following
h-VNS, benefiting an additional 105 per 1000 people compared with l-VNS.
This outcome was limited by
the number of studies available, and the quality of one trial in particular,
wherein 3 people received l-VNS in error. A sensitivity analysis suggested that
the best case scenario was that the likelihood of clinical response to h-VNS may
be 91% (27% to 189%) higher than those receiving l-VNS. In the worst-case
scenario, the likelihood of clinical response to h-VNS was still 61% higher (7%
higher to 143% higher) than l-VNS.
Despite the potential
benefit for h-VNS treatment, the Cochrane review also found that the risk of
several adverse-effects was greater than those receiving l-VNS. There was
moderate certainty of evidence that voice alteration or hoarseness risk may be
2.17(1.49 to 3.17) fold higher than people receiving l-VNS. Dyspnoea risk was
also 2.45 (1.07 to 5.60) times that of l-VNS receipients, although the low
number of events and studies meant that the certainty of evidence was low. The
risk of rebound-withdrawal symptoms, coughing, pain and paraesthesia was
unclear.
Diet
There is promising evidence
that a ketogenic diet (high-fat, low-carbohydrate, adequate-protein) decreases
the number of seizures and eliminates seizures in some; however, further
research is necessary. About 10% stay on
the diet for a few years due to issues of effectiveness and tolerability. Side effects include stomach and intestinal
problems in 30%, and there are long-term concerns about heart disease. Less radical diets are easier to tolerate and
may be effective. It is unclear why this
diet works. In people with celiac
disease or non-celiac gluten sensitivity and occipital calcifications, a
gluten-free diet may decrease the frequency of seizures.
Other
Avoidance therapy consists
of minimizing or eliminating triggers. For example, those who are sensitive to
light may have success with using a small television, avoiding video games, or
wearing dark glasses. Operant-based
biofeedback based on the EEG waves has some support in those who do not respond
to medications. Psychological methods
should not, however, be used to replace medications.
Exercise has been proposed as possibly useful
for preventing seizures, with some data to support this claim. Some dogs, commonly referred to as seizure
dogs, may help during or after a seizure. It is not clear if dogs have the ability to
predict seizures before they occur
There is moderate-quality
evidence supporting the use of psychological interventions along with other
treatments in epilepsy. This can improve
quality of life, enhance emotional wellbeing, and reduce fatigue in adults and
adolescents. Psychological interventions
may also improve seizure control for some individuals by promoting
self-management and adherence
As an add-on therapy in
those who are not well controlled with other medications, cannabidiol appears
to be useful in some children. In 2018 the FDA approved this product for
Lennox–Gastaut syndrome and Dravet syndrome.
There are a few studies on
the use of dexamethasone for the successful treatment of drug-resistant
seizures in both adults and children.
In pregnancy
In women of childbearing
age, use of antiepileptic drugs (AEDs) is a major concern balancing possible
side effects on the fetus against risk from uncontrolled seizures. Use of AEDs
entail teratogenic effects including intrauterine growth retardation, major
congenital malformations and developmental (neurocognitive) and behavioral
issues, that need to be discussed with the patient at the time of starting the
AEDs and before they plan pregnancy. Most
women with epilepsy receive safe and effective treatment and have normal
children, however risks exist. The International League Against Epilepsy
created a task force on women and epilepsy which published consensus
recommendations to guide therapy decisions until more definitive evidence is
available in the future.
Alternative medicine
There is no reliable
evidence to support the use of alternative medicine, including acupuncture,
routine vitamins, and yoga, in epilepsy. The effectiveness of melatonin, as of
2016, is insufficiently supported by evidence.
The trials were of poor methodological quality and it was not possible
to draw any definitive conclusions.
Several supplements (with
varied reliabilities of evidence) have been reported to be helpful for
drug-resistant epilepsy. These include high-dose Omega-3, berberine, Manuka
honey, Reishi and Lion's Mane mushrooms, curcumin, vitamin E, coenzyme Q-10,
and resveratrol. The reason these can work(in theory) is that they reduce
inflammation or oxidative stress, two of the major mechanism contributing to
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 successful 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 ost 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 low income populations or 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.
History
Hippocrates, 17th century
engraving by Peter Paul Rubens of an antique bust
The oldest medical records
show that epilepsy has been affecting people at least since the beginning of
recorded history. Throughout ancient
history, the disease was thought to be a spiritual condition. The
world's oldest description of an epileptic seizure comes from a text in
Akkadian (a language used in ancient Mesopotamia) and was written around 2000
BC. The person described in the text was
diagnosed as being under the influence of a moon god, and underwent an
exorcism. Epileptic seizures are listed
in the Code of Hammurabi (c. 1790
BC) as reason for which a purchased slave may be returned for a refund,[23] and
the Edwin Smith Papyrus (c. 1700
BC) describes cases of individuals with epileptic convulsions.
The oldest known detailed
record of the disease itself is in the Sakikku, a Babylonian cuneiform medical
text from 1067–1046 BC. This text gives
signs and symptoms, details treatment and likely outcomes, and describes many
features of the different seizure types.
As the Babylonians had no
biomedical understanding of the nature of disease, they attributed the seizures
to possession by evil spirits and called for treating the condition through
spiritual means. Around 900 BC,
Punarvasu Atreya described epilepsy as loss of consciousness; this definition
was carried forward into the Ayurvedic text of Charaka Samhita (about 400 BC).
The ancient Greeks had
contradictory views of the disease. They thought of epilepsy as a form of
spiritual possession, but also associated the condition with genius and the
divine. One of the names they gave to it was the sacred disease (ἠ ἱερὰ
νόσος). Epilepsy appears within Greek
mythology: it is associated with the Moon goddesses Selene and Artemis, who
afflicted those who upset them. The Greeks thought that important figures such
as Julius Caesar and Hercules had the disease. The notable exception to this divine and
spiritual view was that of the school of Hippocrates. In the fifth century BC,
Hippocrates rejected the idea that the disease was caused by spirits. In his
landmark work On the Sacred Disease, he proposed that epilepsy was not divine
in origin and instead was a medically treatable problem originating in the
brain. He accused those of attributing a
sacred cause to the disease of spreading ignorance through a belief in
superstitious magic. Hippocrates
proposed that heredity was important as a cause, described worse outcomes if
the disease presents at an early age, and made note of the physical
characteristics as well as the social shame associated with it. Instead of referring to it as the sacred
disease, he used the term great disease, giving rise to the modern term grand
mal, used for tonic–clonic seizures. Despite his work detailing the physical
origins of the disease, his view was not accepted at the time. Evil spirits
continued to be blamed until at least the 17th century.
In Ancient Rome people did
not eat or drink with the same pottery as that used by someone who was
affected. People of the time would spit
on their chest believing that this would keep the problem from affecting them. According to Apuleius and other ancient
physicians, in order to detect epilepsy, it was common to light a piece of
gagates, whose smoke would trigger the seizure. Occasionally a spinning potter's wheel was
used, perhaps a reference to photosensitive epilepsy.
In most cultures, persons
with epilepsy have been stigmatized, shunned, or even imprisoned. As late as in
the second half of the 20th century, in Tanzania and other parts of Africa epilepsy
was associated with possession by evil spirits, witchcraft, or poisoning and
was believed by many to be contagious. In the Salpêtrière, the birthplace of modern
neurology, Jean-Martin Charcot found people with epilepsy side by side with the
mentally ill, those with chronic syphilis, and the criminally insane. In ancient Rome, epilepsy was known as the
morbus comitialis ('disease of the assembly hall') and was seen as a curse from
the gods. In northern Italy, epilepsy was once traditionally known as Saint
Valentine's malady.
In the mid-19th century, the
first effective anti-seizure medication, bromide, was introduced. The first modern treatment, phenobarbital,
was developed in 1912, with phenytoin coming into use in 1938.
Society and culture
Stigma
Stigma is commonly
experienced, around the world, by those with epilepsy. It can affect people economically, socially
and culturally. In India and China,
epilepsy may be used as justification to deny marriage. People in some areas still believe those with
epilepsy to be cursed. In parts of
Africa, such as Tanzania and Uganda, epilepsy is claimed to be associated with
possession by evil spirits, witchcraft, or poisoning and is incorrectly
believed by many to be contagious. Before
1971 in the United Kingdom, epilepsy was considered grounds for the annulment
of marriage. The stigma may result in
some people with epilepsy denying that they have ever had seizures.
Economics
Seizures result in direct
economic costs of about one billion dollars in the United States. Epilepsy resulted in economic costs in Europe
of around 15.5 billion euros in 2004. In
India epilepsy is estimated to result in costs of US$1.7 billion or 0.5% of the
GDP. It is the cause of about 1% of
emergency department visits (2% for emergency departments for children) in the
United States.
Vehicles
See also: Epilepsy and
driving
Those with epilepsy are at
about twice the risk of being involved in a motor vehicular collision and thus
in many areas of the world are not allowed to drive or only able to drive if
certain conditions are met.[2 Diagnostic delay has been suggested to be a cause
of some potentially avoidable motor vehicle collisions since at least one study
showed that most motor vehicle accidents occurred in those with undiagnosed
nonmotor seizures as opposed to those with motor seizures at epilepsy onset. In
some places physicians are required by law to report if a person has had a
seizure to the licensing body while in others the requirement is only that they
encourage the person in question to report it himself. Countries that require
physician reporting include Sweden, Austria, Denmark and Spain. Countries that require the individual to
report include the UK and New Zealand, and physicians may report if they
believe the individual has not already. In Canada, the United States and
Australia the requirements around reporting vary by province or state. If seizures are well controlled most feel
allowing driving is reasonable. The
amount of time a person must be free from seizures before he can drive varies
by country.[205] Many countries require one to three years without seizures. In the United States the time needed without a
seizure is determined by each state and is between three months and one year.
Those with epilepsy or
seizures are typically denied a pilot license. In Canada if an individual has had no more
than one seizure, they may be considered after five years for a limited license
if all other testing is normal. Those
with febrile seizures and drug related seizures may also be considered. In the United States, the Federal Aviation
Administration does not allow those with epilepsy to get a commercial pilot
license. Rarely, exceptions can be made
for persons who have had an isolated seizure or febrile seizures and have
remained free of seizures into adulthood without medication. In the United Kingdom, a full national private
pilot license requires the same standards as a professional driver's license.
This requires a period of ten years without seizures while off medications. Those who do not meet this requirement may
acquire a restricted license if free from seizures for five years.
Support organizations
There are organizations that
provide support for people and families affected by epilepsy. The Out of the
Shadows campaign, a joint effort by the World Health Organization, the
International League Against Epilepsy and the International Bureau for
Epilepsy, provides help internationally. In the United States, the Epilepsy Foundation
is a national organization that works to increase the acceptance of those with
the disorder, their ability to function in society and to promote research for
a cure. The Epilepsy Foundation, some hospitals, and some individuals also run
support groups in the United States. In
Australia, the Epilepsy Foundation provides support, delivers education and
training and funds research for people living with epilepsy.
International Epilepsy Day
(World Epilepsy Day) began in 2015 and occurs on the second Monday in February.
Purple Day, a different
world-wide epilepsy awareness day for epilepsy, was initiated by a
nine-year-old Canadian named Cassidy Megan in 2008 and is every year on March
26.
Research
See also: Computational
models in epilepsy
Seizure prediction and
modeling
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. One of the hypotheses present in the
literature is based on inflammatory pathways. Studies supporting this mechanism
revealed that inflammatory, glycolipid, and oxidative factors are higher in
epilepsy patients, especially those with generalized epilepsy.
Potential future therapies
Gene therapy is being
studied in some types of epilepsy. Medications that alter immune function, such
as intravenous immunoglobulins, are poorly supported by evidence.[221]
Noninvasive stereotactic radiosurgery is, as of 2012, being compared to
standard surgery for certain types of epilepsy.
Jan Ricks Jennings, MHA, LFACHE
Senior Consultant
Senior Management Resources
JanJenningsBlog.Blogspot.com
412.913.0636 Cell
724.733.0509 Home
December 6, 2022
P.S.
On December 6, 1941 Richard Speck December 6, 1941. He was an American mass murderer who killed
eight student nurses in their South Deering, Chicago, residence via stabbing,
strangling, slashing their throats, or a combination of the three on the night
of July 13–14, 1966. One victim was also raped prior to her murder. A ninth
potential victim, student nurse Corazon Amurao, survived by hiding beneath a
bed. Convicted of all eight murders on
April 15, 1967, Speck was sentenced to death. His sentence was reduced to
400–1,200 years in 1972. This was later reduced to 100–300 years. Speck died of
a heart attack while incarcerated at Stateville Correctional Center on the eve
of his 50th birthday.
No comments:
Post a Comment