Made by DATEXIS (Data Science and Text-based Information Systems) at Beuth University of Applied Sciences Berlin
Deep Learning Technology: Sebastian Arnold, Betty van Aken, Paul Grundmann, Felix A. Gers and Alexander Löser. Learning Contextualized Document Representations for Healthcare Answer Retrieval. The Web Conference 2020 (WWW'20)
Funded by The Federal Ministry for Economic Affairs and Energy; Grant: 01MD19013D, Smart-MD Project, Digital Technologies
The mortality rate ranges from 3–7% in a mean follow up period of 8.5 to 9.7 years. Death is often related to accidents.
Dravet syndrome is a severe form of epilepsy. It is a rare genetic disorder that affects an estimated 1 in every 20,000–40,000 births.
LGS is seen in approximately 4% of children with epilepsy, and is more common in males than in females. Usual onset is between the ages of three and five. Children can have no neurological problems prior diagnosis, or have other forms of epilepsy. West syndrome is diagnosed in 20% of patients before it evolves into LGS at about 2 years old.
Like many other types of seizures, gelastic seizures are hard to control for an extended period of time. The best outlook is for children suffering the seizures due to a benign tumor in their hypothalamus. The removal of these tumors can be effective not only for the frequency of the seizures, but also the behavioral and cognitive symptoms that come along with the syndrome. Cases have also been described where that antiepileptic drugs have stopped seizures fully.
Epilepsy is a relatively common disorder, affecting between 0.5-1% of the population, and frontal lobe epilepsy accounts for about 1-2% of all epilepsies. The most common subdivision of epilepsy is symptomatic partial epilepsy, which causes simple partial seizures, and can be further divided into temporal and frontal lobe epilepsy. Although the exact number of cases of frontal lobe epilepsy is not currently known, it is known that FLE is the less common type of partial epilepsy, accounting for 20-30% of operative procedures involving intractable epilepsy. The disorder also has no gender or age bias, affecting males and females of all ages. In a recent study, the mean subject age with frontal lobe epilepsy was 28.5 years old, and the average age of epilepsy onset for left frontal epilepsy was 9.3 years old whereas for right frontal epilepsy it was 11.1 years old.
Studies have found that the incidence of PTE ranges between 1.9 and more than 30% of TBI sufferers, varying by severity of injury and by the amount of time after TBI for which the studies followed subjects.
Brain trauma is one of the strongest predisposing factors for epilepsy development, and is an especially important factor in young adults. Young adults, who are at the highest risk for head injury, also have the highest rate of PTE, which is the largest cause of new-onset epilepsy cases in young people. Children have a lower risk for developing epilepsy; 10% of children with severe TBI and 16–20% of similarly injured adults develop PTE. Being older than 65 is also a predictive factor in the development of epilepsy after brain trauma. One study found PTE to be more common in male TBI survivors than in females.
West syndrome is a triad of developmental delay, seizures termed infantile spasms, and EEG demonstrating a pattern termed hypsarrhythmia. Onset occurs between three months and two years, with peak onset between eight and 9 months. West syndrome may arise from idiopathic, symptomatic, or cryptogenic causes. The most common cause is tuberous sclerosis. The prognosis varies with the underlying cause. In general, most surviving patients remain with significant cognitive impairment and continuing seizures and may evolve to another eponymic syndrome, Lennox-Gastaut syndrome. It can be classified as idiopathic, syndromic, or cryptogenic depending on cause and can arise from both focal or generalized epileptic lesions.
The National Institute of Health Office and Rare Disease Research characterizes PCDH19 gene-related epilepsy as a rare disorder. Rare diseases, by definition, are diseases that affect fewer than 200,000 people in the United States. Since the mutation associated with PCDH19 gene-related epilepsy was only recently identified in 2008, the true incidence of the disease is generally unknown.
Although formal epidemiologic data is not available, results from diagnostic screening indicates that approximately 1 out of 10 girls who have seizure onset before five years of age may have PCDH19 gene mutations. Additionally, PCDH19 screening of several large cohorts of females with early onset febrile-related epilepsy has resulted in a rate of approximately 10% of mutation-positive individuals.
Both medication and drug overdoses can result in seizures, as may certain medication and drug withdrawal. Common drugs involved include: antidepressants, antipsychotics, cocaine, insulin, and the local anaesthetic lidocaine. Difficulties with withdrawal seizures commonly occurs after prolonged alcohol or sedative use, a condition known as delirium tremens.
The prognosis for epilepsy due to trauma is worse than that for epilepsy of undetermined cause. People with PTE are thought to have shorter life expectancies than people with brain injury who do not suffer from seizures. Compared to people with similar structural brain injuries but without PTE, people with PTE take longer to recover from the injury, have more cognitive and motor problems, and perform worse at everyday tasks. This finding may suggest that PTE is an indicator of a more severe brain injury, rather than a complication that itself worsens outcome. PTE has also been found to be associated with worse social and functional outcomes but not to worsen patients' rehabilitation or ability to return to work. However, people with PTE may have trouble finding employment if they admit to having seizures, especially if their work involves operating heavy machinery.
The period of time between an injury and development of epilepsy varies, and it is not uncommon for an injury to be followed by a latent period with no recurrent seizures. The longer a person goes without developing seizures, the lower the chances are that epilepsy will develop. At least 80–90% of people with PTE have their first seizure within two years of the TBI. People with no seizures within three years of the injury have only a 5% chance of developing epilepsy. However, one study found that head trauma survivors are at an increased risk for PTE as many as 10 years after moderate TBI and over 20 years after severe TBI. Since head trauma is fairly common and epilepsy can occur late after the injury, it can be difficult to determine whether a case of epilepsy resulted from head trauma in the past or whether the trauma was incidental.
The question of how long a person with PTE remains at higher risk for seizures than the general population is controversial. About half of PTE cases go into remission, but cases that occur later may have a smaller chance of doing so.
Dehydration can trigger epileptic seizures if it is severe enough. A number of disorders including: low blood sugar, low blood sodium, hyperosmolar nonketotic hyperglycemia, high blood sodium, low blood calcium and high blood urea levels may cause seizures. As may hepatic encephalopathy and the genetic disorder porphyria.
Temporal lobe epilepsy (TLE) is not a classic syndrome but mentioned here because it is the most common epilepsy of adults. It is a symptomatic localization-related epilepsy and in most cases the epileptogenic region is found in the midline (mesial) temporal structures (e.g., the hippocampus, amygdala, and parahippocampal gyrus). Seizures begin in late childhood and adolescence. Most of these patients have focal seizures sometimes preceded by an aura, and some TLE patients also have secondary generalized tonic-clonic seizures. Often seizures do not sufficiently respond to medical treatment with anticonvulsants and epilepsy surgery may be considered.
Benign familial infantile epilepsy (BFIE), also known as benign familial infantile seizures (BFIS) or benign familial infantile convulsions (BFIC) is an epilepsy syndrome. Affected children, who have no other health or developmental problems, develop seizures during infancy. These seizures have focal origin within the brain but may then spread to become generalised seizures. The seizures may occur several times a day, often grouped in clusters over one to three days followed by a gap of one to three months. Treatment with anticonvulsant drugs is not necessary but they are often prescribed and are effective at controlling the seizures. This form of epilepsy resolves after one or two years, and appears to be completely benign. The EEG of these children, between seizures, is normal. The brain appears normal on MRI scan.
A family history of epilepsy in infancy distinguishes this syndrome from the non-familial classification (see benign infantile epilepsy), though the latter may be simply sporadic cases of the same genetic mutations. The condition is inherited with an autosomal dominant transmission. There are several genes responsible for this syndrome, on chromosomes 2, 16 and 19. It is generally described as idiopathic, meaning that no other neurological condition is associated with it or causes it. However, there are some forms that are linked to neurological conditions. One variant known as infantile convulsions and choreoathetosis (ICCA) forms an association between BFIE and paroxysmal kinesigenic choreoathetosis and has been linked to the PRRT2 gene on chromosome 16. An association with some forms of familial hemiplegic migraine (FHM) has also been found. Benign familial infantile epilepsy is not genetically related to benign familial neonatal epilepsy (BFNE), which occurs in neonates. However, a variation with seizure onset between two days and seven months called "benign familial neonatal–infantile seizures" (BFNIS) has been described, which is due to a mutation in the SCN2A gene.
No single cause of OS has been identified. In most cases, there is severe atrophy of both hemispheres of the brain. Less often, the root of the disorder is an underlying metabolic syndrome. Although it was initially published that no genetic connection had been established, several genes have since associated with Ohtahara syndrome. It can be associated with mutations in "ARX", "CDKL5", "SLC25A22", "STXBP1", "SPTAN1", "KCNQ2", "ARHGEF9", "PCDH19", "PNKP", "SCN2A", "PLCB1", "SCN8A", and likely others.
Treatment outlook is poor. Anticonvulsant drugs and glucocorticoid steroids may be used to try to control the seizures, but their effectiveness is limited. Most therapies are related to symptoms and day-to-day living.
Gelastic seizures are usually not responsive to pharmacotherapy. They can produce secondary seizure characteristics which may respond to medications or surgery. These options are not a guaranteed cure, and depend primarily on the individual patient’s pathology.
The treatment depends on the cause of the seizures. If the seizures are caused by a tumor, surgical removal can be attempted. However, surgical removal is not always an immediate cure, and there can be complications. Complications can include cerebral infarcts, and cognitive deterioration. Hormonal treatment can be attempted to help individuals with precocious puberty. Anti-epileptic drugs could be an option as well depending on the patient’s criteria. These drugs could include carbamazepine, clobazam, lamotrigine, levetiracetam, oxcarbazepine and topiramate. However, usually none of these medications are capable of stopping the seizures from occurring, and like any medication, there may be undesirable side effects. There is also a specialized form of radiotherapy that may be an option depending on the tumor type and location. Once again, there are very few areas in the world that offer this treatment. Gamma knife radiosurgery can be the treatment of choice when it comes to hypothalamic hamartomas. It is a low risk option due to its lower frequency of neurological deficits. It is recommended for patients with tumors that don’t come into contact with the optic chiasm.
There have been early and consistent strategies for measurement to better understand vertiginous epilepsy including caloric reflex test, posture and gait, or rotational experimentation.
In Japan, Kaga et al prepared a longitudinal study of rotation tests comparing congenital deafness and children with delayed acquisition of motor system skills. They were able to demonstrate the development of post-rotation nystagmus response from the frequency of beat and duration period from birth to six years to compare to adult values. Overall, the study demonstrated that some infants from the deaf population had impaired vestibular responses related to head control and walking age. A side interpretation included the evaluation of the vestibular system in reference to matching data with age.
Research in this area of medicine is limited due to its lacking need for urgent attention. But, the American Hearing Research Foundation (AHRF) conducts studies in which they hope to make new discoveries to help advance treatment of the disease and possibly one day prevent vertiginous seizures altogether.
A 2008 study, found a relationship between the PCDH19 gene and early onset female seizures, with subsequent studies confirming the relationship.
PCDH19 gene-related epilepsy can arise as a single case in a family, due to a de novo error in cell replication, or it can be inherited. In a large series of cases in which inheritance was determined, half of the PCDH19 mutations occurred de novo, and half were inherited from fathers in good health, and who had no evidence of seizures or cognitive disorders.
Men and women can transmit the PCDH19 mutation, although females, but not males, usually, but not always, exhibit symptoms, which can be very mild. Females with a mutation have a 50% chance of having children who are carriers. Men have a 100% chance of transmitting the mutation to a daughter and 0% chance to a son.
Although males do not generally exhibit PCDH19 gene-related history such as cluster seizures, in a study involving four families with PCDH19 gene mutations, 5 of the fathers had obsessive and controlling tendencies. The linkage of chromosome Xq22.1 to PCDH19 gene-related epilepsy in females was confirmed in all of the families.
The inheritance pattern is very unusual, in that men that carry the PCDH19 gene mutation on their only X-chromosome are typically unaffected, except in rare instances of somatic mosaicism. Alternatively, approximately 90% of women, who have the mutation on one of their two X-chromosomes, exhibit symptoms. It has been suggested that the greater occurrence of PCDH19-epilepsy in females may relate to X-chromosome inactivation, through a hypothesized mechanism termed ‘‘cellular interference’’.
A 2011 study found instances where patients had PCDH19 mutation, but their parents did not. They found that "gonadal mosaicism” of a PCDH19 mutation in a parent is an important molecular mechanism associated with the inheritance of a mutated PCDH19 gene.
Most generalized epilepsy starts during childhood. While some patients outgrow their epilepsy during adolescence and no longer need medication, in others, the condition remains for life, thereby requiring lifelong medication and monitoring.
These syndromes are childhood absence epilepsy, epilepsy with myoclonic absences, juvenile absence epilepsy and juvenile myoclonic epilepsy. Other proposed syndromes are Jeavons syndrome (eyelid myoclonia with absences), and genetic generalised epilepsy with phantom absences.
These types of seizures are also known to occur to patients suffering with porphyria and can be triggered by stress or other porphyrin-inducing factors.
Although the theory is controversial, there is a link between febrile seizures (seizures coinciding with episodes of fever in young children) and subsequent temporal lobe epilepsy, at least epidemiologically.
Seven anti-epileptic drugs are approved for use in cases of suspected primary generalized epilepsy:
- Felbamate
- Levetiracetam
- Zonisamide
- Topiramate
- Valproate
- Lamotrigine
- Perampanel
Valproate, a relatively old drug, is often considered the first-line treatment. It is highly effective, but its association with fetal malformations when taken in pregnancy limits its use in young women.
All anti-epileptic drugs (including the above) can be used in cases of partial seizures.
Treatment is in the form of anti-epileptic drugs, such as barbiturates, benzodiazepines and topiramate.
Unfortunately, there is no real way to prevent against vertiginous episodes out of the means of managing the disease. As head trauma is a major cause for vertiginous epilepsy, protecting the head from injury is an easy way to avoid possible onset of these seizures. With recent advances in science it is also possible for an individual to receive genetic screening, but this only tells if the subject is predisposed to developing the condition and will not aid in preventing the disease.
There is a range of ways to manage vertiginous epilepsy depending on the severity of the seizures. For simple partial seizures medical treatment is not always necessary. To the comfort of the patient, someone ailed with this disease may be able to lead a relatively normal life with vertiginous seizures. If, however, the seizures become too much to handle, antiepileptic medication can be administered as the first line of treatment. There are several different types of medication on the market to deter epileptic episodes but there is no support to show that one medication is more effective than another. In fact, research has shown that simple partial seizures do not usually respond well to medication, leaving the patient to self-manage their symptoms. A third option for treatment, used only in extreme cases when seizure symptoms disrupt daily life, is surgery wherein the surgeon will remove the epileptic region.
Between 10 and 30% of people who have status epilepticus die within 30 days. The great majority of these people have an underlying brain condition causing their status seizure such as brain tumor, brain infection, brain trauma, or stroke. However, people with diagnosed epilepsy who have a status seizure also have an increased risk of death if their condition is not stabilized quickly, their medication and sleep regimen adapted and adhered to, and stress and other stimulant (seizure trigger) levels controlled.
However, with optimal neurological care, adherence to the medication regimen, and a good prognosis (no other underlying uncontrolled brain or other organic disease), the person—even people who have been diagnosed with epilepsy—in otherwise good health can survive with minimal or no brain damage, and can decrease risk of death and even avoid future seizures.
Epilepsy has a substantial impact on the quality of life of the individuals that are afflicted with it. Physicians and researchers are coming to understand that the impact on the quality of life of the patient is as important as the effects of the seizures. Quality of life questionnaires and other assessment tools have been created to help quantify quality of life for individual patients. They consider such factors as physical health (including numbers and severity of seizures, medication side effects etc.), mental health, social relationships, lifestyle, role activities and life fulfillment. A Center for Disease Control study reported that seizure sufferers were more likely to have lower education levels, higher unemployment, higher levels of pain, hypersomnia/insomnia, increased psychological distress and social isolation/connection issues. Some of the issues which impact quality of life for people with epilepsy are: ability to drive and travel, the ability to date, marry and have children, the ability to have a job and independence, the ability to have an education and learn, and the ability to have good health and mental functioning. Future research is needed to find ways of not only controlling frontal lobe seizures, but of also addressing the specific quality-of-life issues that plague those with frontal lobe epilepsy.
- Driving and transportation restrictions
- Driving and travel restrictions are one of the greatest limitations that epileptic patients experience. Laws restricting driving privileges vary greatly in the United States as well as across the world. In the United States, 28 states require a patient to be seizure free for fixed periods of time ranging from 3–12 months. However, research done by Johns Hopkins University showed that there was no difference in seizure-related fatal crash rates in states with 3-month restrictions versus states with 6-12 month seizure-free restrictions. In 23 states, the restrictions and seizure free periods vary depending on the type of epilepsy and the individual case and in 13 states physicians were responsible for determining whether their patients should be allowed to drive. In 6 of those 13 states physicians could be held legally liable for their decisions regarding their epileptic patients’ driving capabilities. In many states, patients can also be legally liable for accidents, injury, damage and death caused by seizure related accidents.
- One of the major arguments in favor of restricting the licensing of epileptic drivers is the concern for public safety. However, the Johns Hopkins study showed that in a particular 2 year timeframe only 0.2% of fatal crashes occurred as a result of seizures. Alcohol related crash fatalities caused 156 times more driver deaths than seizure related crashes and young drivers between the ages of 16 and 24 were 123 times more likely to die in a fatal crash caused by their inexperience than an epileptic driver was to die in a crash that resulted from a seizure.
- Frontal lobe epileptic seizures unlike other epileptic seizures create symptoms that are as dangerous as loss of consciousness and much more difficult to discern from other problems such as drug and alcohol abuse, psychiatric disorders and disobedience. Jerking movements/lack of motor control, pedaling, pelvic thrusting, lapses in cognitive functioning and other hallmark symptoms of frontal lobe epileptic seizures all create dangerous behavior behind the wheel. Studies have not been done to date to determine the differential risk posed by drivers with frontal lobe epilepsy relative to the general epileptic population.
- Hormones and pregnancy issues
- Hormonal changes and pregnancy can shift seizure activity and the use of antiepileptic drugs can alter the efficacy of hormones as well as cause congenital malformations in fetuses. Seizure control in pregnant women is very important to the welfare of both the developing fetus and the mother. Hormonal shifts at puberty, with birth control and at menopause can also cause changes in the frequency and severity of seizures and must be closely monitored. Increased seizure activity is reported by 50% of women during the course of the pregnancy due to changing levels of hormones, fluids, salts and absorption and elimination of medications.
- Employment
- A report by the Epilepsy Foundation noted that the unemployment rate amongst people with epilepsy is 25% and in patients whose seizures are poorly controlled the rate jumps to 50%. Even though people with epilepsy are protected under The Americans with Disabilities Act, employment discrimination and high rates of unemployment due to employer attitudes still exist. A study in the UK showed that 16% of employers surveyed felt there were no jobs in their company suitable for people with epilepsy and that 21% felt that employing an epileptic would be a “major issue”. Fifty percent of the employers said they had a high concern regarding employing people with epilepsy with most citing safety concerns/workplace accidents as their major issue. Patients with frontal lobe epilepsy may be particularly prone to being discriminated against in employment and subject to higher rates of termination due to the unusual motor symptoms, speech, vocal outbursts and cognitive/judgment symptoms displayed during frontal lobe seizures. Frontal lobe seizures also tend to come on suddenly and progress rapidly making it difficult for an employer to control the exposure of the seizure to others.
- Education, learning and cognitive function
- Patients with frontal lobe epilepsy will likely also experience issues with learning and education. Many factors contribute to these issues including the impact of anticonvulsant medications. Anticonvulsant medications cause patients to feel “foggy” and sluggish. Drugs such as Topiramate cause problems such as mental blunting, word retrieval difficulties and irritability. Phenobarbital, Primidone and Vigabatrin can cause depression and suicidal tendencies. Stress and lack of sleep during exam periods can trigger seizures and many school sports teams restrict or ban people with epilepsy from sports for safety and liability reasons. Frontal lobe epilepsy sufferers also exhibit dysfunctional cognitive skills and memory issues which can make learning challenging. Research has shown that frontal lobe epilepsy has a greater negative impact than other forms of epilepsy on cognitive functioning. People with frontal lobe epilepsy show decreased cognitive capabilities in the following areas: humor appreciation, recognition of emotional expressions, response selection/initiation and inhibition, hyperactivity, conscientiousness, obsession, addictive behavior, motor coordination and planning, attention span, performance speed, continuous performance without intrusion and interference errors, copying and recall, concept formation, anticipatory behavior, memory span, working memory, executive planning, visuo-spatial organization, mental flexibility, conceptual shift, problem solving, programming of complex motor sequences, impulse control, judgment and forecasting of consequences.
- Physical health and risk of other conditions
- Patients with epilepsy face a greater risk of accidents, injury and other medical conditions than the general population. A European study showed that people with epilepsy were at greater risk for accidental injuries related to seizures such as concussions, abrasions and wounds and reported more hospitalizations and medical action than the general population. Other studies have shown that people with epilepsy are at a greater risk of seizure related drowning, suffocation, broken bones and burns and more likely to die in a fatal automobile crash.
- Epilepsy Ontario reports that people with epilepsy are also more likely to have other conditions than the general population such as: 30% of autistic children have epilepsy, 33% of cerebral palsy patients have epilepsy, 15-20% of fragile X syndrome patients have epilepsy, 50% of children with learning disabilities will have some form of epilepsy, 3-10% of patients with Lennox-Gastaut syndrome will have epilepsy, 80% of children with Rett syndrome will have epilepsy and 80% of patients with Tuberous Sclerosis will have epilepsy.
- Mental and emotional health
- Epileptic patients are more prone to suffer psychological and social dysfunction than individuals that do not have epilepsy. They report higher levels of anxiety and stress due to social isolation, discrimination, the unpredictability of their seizures and people’s reactions to them as well as fear of injury, death and brain damage from their seizures. Anticonvulsants can also result in lower functioning, depression, sluggishness and suicidal thoughts. Approximately 20% of people with epilepsy are depressed and the rate of suicide amongst people with epilepsy is 5 times the rate in the general population.
- People with frontal lobe epilepsy experience more significant social effects because the manifested symptoms are more unusual. Symptoms such as screaming, bicycling limbs, pelvic thrusting, inhibition control and other outbursts can be particularly embarrassing and isolating for the patient.