French scientists say they have proof that dogs can pick up the smell of an epileptic seizure. The University of Rennes team hope the findings could lead to ways to predict when people will have a seizure.
These could include dogs or “electronic noses” that pick up the precise odour being given off during a seizure.
Dogs have previously been shown to be able to sniff out diseases including cancers, Parkinson’s, malaria and diabetes.
Epilepsy is caused by disruption to the electrical signals in the brain causing seizures
The disease can run in families or be caused by a stroke or oxygen deprivation at birth
Some people with epilepsy already rely on the animals.
One sleeping in a child’s bedroom can alert family members of a seizure in the middle of the night.
The latest study, in the journal Scientific Reports, trained five dogs from Medical Mutts, in the US, to recognise the smell of sweat taken from a patient having a seizure.
They were then given a choice of seven sweat samples taken from other patients while they were either relaxing, exercising or having a seizure.
Two of the dogs found the seizure sample about two-thirds of the time and the other three were 100% accurate
The report says: “The results are extremely clear and constitute a first step towards identifying a seizure-specific odour.”
That would require detailed chemical analysis to identify the specific compounds involved.
It is also unknown how an epileptic seizure leads to a change in smell.
Dr Amelie Catala, from the University of Rennes said: “Further research is needed but it is possible that the change in electrical activity triggers the releasing of some neurohormones that will in the end trigger the scent or that it is linked to stress-related molecules and pathways, or anything else – all hypothesis are still to be considered.”
But the researchers hope the field could eventually help patients.
“It could lead to significant improvements in terms of seizure detection or prediction systems,” the report adds.
And that could give time for someone to call for help or get themselves somewhere safe before their seizure begins.
Epilepsy is a disorder of the brain characterized by repeated seizures. A seizure is usually defined as a sudden alteration of behavior due to a temporary change in the electrical functioning of the brain. Normally, the brain continuously generates tiny electrical impulses in an orderly pattern. These impulses travel along neurons — the network of nerve cells in the brain — and throughout the whole body via chemical messengers called neurotransmitters.
In epilepsy the brain’s electrical rhythms have a tendency to become imbalanced, resulting in recurrent seizures. In patients with seizures, the normal electrical pattern is disrupted by sudden and synchronized bursts of electrical energy that may briefly affect their consciousness, movements or sensations.
Epilepsy is usually diagnosed after a person has had at least two seizures that were not caused by some known medical condition, such as alcohol withdrawal or extremely low blood sugar.
If seizures arise from a specific area of the brain, then the initial symptoms of the seizure often reflect the functions of that area. The right half of the brain controls the left side of the body, and the left half of the brain controls the right side of the body. For example, if a seizure starts from the right side of the brain in the area that controls movement in the thumb, then the seizure may begin with jerking of the left thumb or hand.
Types of epileptic seizures
Seizures vary so much that epilepsy specialists frequently re-classify seizure types. Typically, seizures belong in one of two basic categories: primary generalized seizures and partial seizures. The difference between these types is in how they begin. Primary generalized seizures begin with a widespread electrical discharge that involves both sides of the brain at once. Partial seizures begin with an electrical discharge in one limited area of the brain.
Epilepsy in which the seizures begin from both sides of the brain at the same time is called primary generalized epilepsy. Hereditary factors are important in partial generalized epilepsy, which is more likely to involve genetic factors than partial epilepsy — a condition in which the seizures arise from a limited area of the brain.
Some partial seizures are related to head injury, brain infection, stroke or tumor but, in most cases, the cause is unknown. One question that is used to further classify partial seizures is whether consciousness (the ability to respond and remember) is impaired or preserved. The difference may seem obvious, but there are many degrees of consciousness impairment or preservation.
The following factors may increase the risk of seizures in people predisposed to seizures:
Sleep deprivation or fatigue
Insufficient food intake
Alcohol use or drug abuse
Failure to take prescribed anticonvulsant medications
About half of the people who have one seizure without a clear cause will have another one, usually within six months. A person is twice as likely to have another seizure if there is a known brain injury or other type of brain abnormality. If the patients does have two seizures, there is about an 80 percent chance of having more. If the first seizure occurred at the time of an injury or infection in the brain, it is more likely the patient will develop epilepsy than if the seizure did not happen at the time of injury or infection.
Epilepsy: Prevalence and Incidence
According to the Epilepsy Foundation, epilepsy affects three million people in the U.S. and 50 million worldwide. Epileptic seizures may be tied to a brain injury or genetics, but for 70 percent of epilepsy patients, the cause is unknown. The Epilepsy Therapy Project notes that 10 percent of people will have seizures in their lifetime.
Epilepsy affects more than 300,000 children under the age of 15 — and more than 90,000 young people in this group have seizures that cannot be adequately treated. The onset rate starts to increase when individuals age, particularly as they develop strokes, brain tumors or Alzheimer’s disease, all of which may cause epilepsy. Reports indicate that more than 570,000 adults over the age of 65 suffer from the disorder.
More men than women have epilepsy. Children and adolescents are more likely to have epilepsy of unknown or genetic origin. Brain injury or infection can cause epilepsy at any age. The Epilepsy Foundation also reports that 70 percent of children and adults with newly diagnosed epilepsy can be expected to enter remission after having gone five years or more without a seizure while on medication. In addition, 75 percent of people who are seizure-free on medication can be weaned from medication eventually. According to the National Institute of Neurological Disorders and Stroke, 20 percent of epilepsy patients have intractable seizures — seizures that do not respond to treatment.
The reasons why epilepsy begins are different for people of different ages. But what is known is that the cause is undetermined for about half of all individuals with epilepsy, regardless of age. Children may be born with a defect in the structure of their brain or they may suffer a head injury or infection that causes their epilepsy. Severe head injury is the most common known cause in young adults. For middle-age individuals, strokes, tumors and injuries are more frequent catalysts. In people age 65 and older, stroke is the most common known cause, followed by degenerative conditions such as Alzheimer’s disease. Often, seizures do not begin immediately after a person has an injury to the brain. Instead, a seizure may occur many months later.
Epilepsy Risk Factors
Premature birth or low birth weight
Trauma during birth (such as lack of oxygen)
Seizures in the first month of life
Abnormal brain structures at birth
Bleeding into the brain
Abnormal blood vessels in the brain
Serious brain injury or lack of oxygen to the brain
Infections of the brain such as meningitis or encephalitis
Stroke resulting from blockage of arteries
Seizures occurring within days after head injury
Family history of epilepsy or fever-related seizures
Alzheimer’s disease (late in the illness)
Lengthy fever-related (febrile) seizures
Alcohol or drug abuse
A doctor makes his or her epilepsy diagnosis based on symptoms, physical signs and the results of such tests as an electroencephalogram (EEG), computed tomography (CT or CAT scan) or magnetic resonance imaging (MRI).
It is essential that the type of epilepsy and the type of seizures both are diagnosed properly. There are several major classifications of seizures and most are associated with specific forms of the disorder.
Epilepsy may be treated with antiepileptic medications (AEDs), diet therapy and surgery. Medications are the initial treatment choice for almost all patients with multiple seizures. Some patients who only have a single seizure and whose tests do not indicate a high likelihood of seizure recurrence may not need medications. The medications treat the symptoms of epilepsy (the seizures), rather than curing the underlying condition. They are highly effective and completely control seizures in the majority (approximately 70%) of patients. The drugs prevent seizures from starting by reducing the tendency of brain cells to send excessive and confused electrical signals.
With many different antiepileptic drugs currently available, choosing the right medication for an individual patient has become complicated. Choice of medication depends on a variety of factors, some of which include the type of seizure and type of epilepsy, the likely side effects of the medication, other medical conditions the patient may have, potential interactions with the patient’s other medications, age, gender and cost of the medication.
Before any drug is prescribed, patients should discuss potential benefits, side effects and risks with their doctors.
Diet therapy may be utilized in some patients with specific forms of epilepsy. The most common diets utilized are the ketogenic diet and the modified Atkins diet. The ketogenic diet is a special high-fat, adequate protein and low carbohydrate diet that is initiated over three to four days in the hospital. The modified Atkins diet is similar to the ketogenic diet but is slightly less restrictive. It can be initiated as an outpatient. Both diets have been shown to reduce seizures in approximately half the patients that are identified to be appropriate candidates. These are mainly children with refractory epilepsy who are not surgical candidates.
While approximately 70 percent of patients have well-controlled seizures with these modalities, the remaining 30 percent do not and are considered medically-resistant. Patients with medically-resistant epilepsy are often treated at specialized epilepsy centers in a multi-disciplinary fashion.
The team of trained specialists that collaborate to provide these patients with comprehensive diagnosis and treatment of epilepsy may include:
Epilepsy nurse practitioners
Nuclear medicine radiologists
In patients whose seizures are medically resistant, surgery provides the best chance of complete control of seizures. However, not all patients with refractory epilepsy are suitable candidates for surgery. In addition to being refractory, they need to have partial, rather than generalized epilepsy (i.e. their epilepsy arises from a single part of the brain, rather than from both sides or from all over the brain).
Furthermore, the epileptic region should be in a part of the brain that, if removed, is unlikely to result in major neurological complications. Whether or not patients are likely to benefit from surgery is determined by detailed testing (pre-surgical evaluation).
Pre-surgical evaluation consists of a one- or two-phase process to determine if surgery is the best option and can provide good seizure control with minimal risk. Phase I involves all non-invasive (non-surgical) tests. Phase II testing involves invasive tests (requires surgery) that are used in select patients.
Phase I Evaluation (noninvasive tests)
Not every patient requires every test available in the Phase I evaluation. Adult and pediatric epilepsy patients are evaluated by epileptologists who determine the necessary and appropriate tests on an individualized basis. The following tests may be required in the phase I evaluation:
This is the initial test performed in every patient and is usually done as an outpatient procedure (pictured here). It is used not only to diagnose epilepsy, but also to determine if the epileptic seizures are coming from a small part of the brain (partial seizures), or all over the brain ( generalized).
Although most patients do not have seizures when the EEG is being recorded, they often have abnormal brain activity in the EEG (spikes or sharp waves) that indicates they have a tendency to have seizures. The location of this activity allows the physician to determine whether patients have partial or generalized seizures.
Inpatient Video-EEG monitoring in Adult and Pediatric Epilepsy monitoring Units (EMU)
This is the most important pre-surgical test and is performed with electrodes attached to the scalp (noninvasive monitoring). Patients are admitted to the hospital for several days and the purpose is to record seizures with simultaneous video and EEG. All the data are analyzed by a trained epileptologist. Detailed analysis of the symptoms during seizures as well as the location of EEG changes during seizures (ictal EEG onset), and abnormalities noted in between seizures (interictal), indicate the likely location where seizures originate within the brain.
Magnetic Resonance Imaging (MRI)
This may detect an abnormality that could be the cause of the epilepsy (lesional epilepsy) or may be normal (non-lesional epilepsy). With more powerful MRI machines and use of special protocols and software, subtle brain abnormalities are increasingly being identified.
Positron emission tomography (PET)
PET scans look at the metabolic activity of the brain and allow physicians to determine if the brain is functioning normally. In patients with epilepsy, decreased brain function is seen in the region where seizures originate, when the patient is not actually having a seizure. On the other hand, if the patient has a seizure during the test, increased brain function is seen. PET scan may show abnormalities even if the brain MRI is normal. PET scans are usually done in the outpatient setting.
Single-photon emission computed tomography (SPECT)
When a person has a seizure, an increased amount of blood flows to the brain region where the seizure begins. SPECT scans performed during seizures can identify the brain region where blood flow increases and thus indicate where they begin. SPECT scans are performed when the patient is admitted to the hospital for video-EEG monitoring.
Neuropsychological evaluation, functional MRI: Neuropsychological evaluation and functional MRI are used to assess cognitive functions, especially language and memory function prior to surgery, to see which side of the brain is dominant for language and to determine if there is decreased memory function in the epileptic region. This allows prediction of cognitive deficits after surgery. Functional MRI (fMRI) measures blood flow changes in areas of the brain during the performance of specific cognitive tasks.
Intracarotid amobarbital/methohexital (Wada test)
This test involves the injection of a medication such as sodium amobarbital or methohexital into one carotid artery at a time and is performed in selected cases. The medication causes temporary (1-5 minutes) paralysis of one half of the brain allowing independent testing of language and memory function in the other half. This test is also used to predict post-operative deficits in language and memory function.
Results of video-EEG monitoring are compared with those obtained from the other tests to see if they all point to the same region of the brain as being the origin of epileptic seizures. If all the test results are concordant, the patient is likely to be a good surgical candidate. Thus, the Phase I evaluation is designed to find the area of the brain that is likely to be generating the seizures (the focus), to determine if that area can be safely removed, and predict what kind of outcome might be expected with regard to seizure reduction or seizure freedom.
After the Phase I evaluation, the epilepsy team meets to discuss patient management options in a multi-disciplinary setting to individualize treatments. At that time, based on the results of the Phase I evaluation, patients may be deemed good or poor surgical candidates. In some cases, it may be unclear and more testing is needed. This additional testing is called Phase II evaluation and is performed in select cases, where despite all prior tests, the seizure focus is not defined well enough for surgical treatment.
Phase II evaluation involves video-EEG monitoring with electrodes that are placed inside the skull (invasive monitoring). As there is more risk from invasive monitoring, the decision about the necessity for a Phase II evaluation is usually made by the epilepsy team as a whole and discussed in detail with the patient.
Phase II Evaluation
There are several surgical implantation options. Each involves the implantation of electrodes either on the surface of the brain, or within the brain. The benefit of these electrodes is that they are closer to the area producing the seizures than those placed simply on the scalp. After surgical placement of electrodes, the patients are transferred to the epilepsy monitoring unit and epileptologists perform video- EEG monitoring in a similar fashion to the phase I monitoring.
The electrode types and implantation arrays differ and may include:
A subdural electrode grid is a thin sheet of material with multiple small (couple millimeters in size) recording electrodes implanted within it. These are placed directly on the surface of the brain and have the advantage of recording the EEG without the interference of skin, fat tissue, muscle and bone that may limit scalp EEG. Shapes and sizes of these sheets are chosen to best conform to the surface of the brain and the area of interest.
These are small wires which are implanted within the brain itself. Each wire has electrodes which surround it. These electrodes are able to record brain activity along the entire length of the implanted wire. They have the advantage of recording activity from structures deeper in the brain. They can be implanted through small skin pokes.
In a number of instances, it is beneficial to implant a combination of subdural electrodes and depth electrodes.
Increasingly common, invasive monitoring may be done using the stereoelectroencephalography approach (stereoEEG). With this approach, multiple depth electrodes are implanted in a specific pattern that is individualized to the patient. The three-dimensional space which is covered by the depth electrodes is designed to encompass the seizure focus.
This is usually performed in patients with implanted subdural electrodes while they are in the EMU. After a sufficient number of seizures are recorded, brief electrical stimulation is provided through each electrode separately to determine the normal function of the part of the brain underneath the electrode. This is painless. The purpose is to map out critically important areas of the brain such as those necessary for motor, sensory and language functions and to determine if there is any overlap with the seizure-generating regions. This allows tailoring of surgical resections to minimize the risk of major neurological deficits after surgery.
Surgery for the treatment of epilepsy involves resection, disconnection, stereotactic radiosurgery or implantation of neuromodulation devices. Within these categories, there are multiple options depending on the clinical scenario.
Surgical resection (removal of abnormal tissue) for epilepsy may fall into the following broad categories:
A lesion is a generic term for brain abnormalities that show up on imaging. Some types of lesions — such as cavernous malformations (blood vessel abnormality) and tumors — are prone to cause seizures. When the pre-operative testing indicates that these lesions are the cause of the epilepsy, they can be removed surgically.
Each hemisphere, or half, of the brain is divided into four main lobes — the frontal, temporal, parietal and occipital. Seizures may arise within any of the lobes. A lobectomy is an operation to remove a lobe of the brain. Removal of one of the temporal lobes — called a temporal lobectomy — is the most common type of epilepsy surgery performed. Other types of lobectomies may rely on more specialized testing and surgery to prove a lack of vital function (such as speech, memory, vision, motor function).
A multilobar resection involves removal of parts or all of two or more lobes of the brain. It is reserved for more widespread abnormalities causing seizures, providing that no vital functions are in those regions.
The brain is divided into a left and right hemisphere. In rare instances, children may have severe, uncontrollable and devastating seizures that can be associated with weakness on one side of the body. This may occur with a large amount of damage or injury to one of the hemispheres. Surgery to remove or disconnect a hemisphere, a hemispherectomy may be curative. There are many subtypes of this surgery, the two main divisions being anatomic and functional hemispherectomy. Anatomic hemispherectomy involves removing the entire half of the brain that is injured and is generating the debilitating seizures. This includes the four lobes of the hemisphere — frontal, temporal, parietal and occipital. Functional hemispherectomy involves separating the abnormal hemisphere from the normal one by disconnecting fibers that communicate between the two. Often, some portions of the abnormal brain are surgically removed in order to perform this disconnection.
Functional hemispherectomy involves separating the abnormal hemisphere from the normal one by disconnecting fibers that communicate between the two. Often, some portions of the abnormal brain are surgically removed in order to perform this disconnection. This is, very often, surgically curative.
These surgeries involve cutting and dividing fiber bundles that connect portions of the brain. The rationale is to separate the area of the brain generating the seizures from the normal brain.
The corpus callosum is one of the main fiber bundles that connect the two hemispheres. When debilitating generalized seizures or falling-type seizures start on one side of the brain and quickly spread to the other, patients may be candidates for this procedure. A large part of this fiber bundle may be cut. The procedure is palliative, meaning that although seizures may improve, they usually do not disappear.
Multiple subpial transections (MST)
In certain cases of epilepsy, where the seizures are deemed to be arising from an area of the brain that cannot be safely removed, multiple subpial transections can be performed. In this procedure, a small wire is placed into the brain to perform transections at multiple points in a given region which can decrease seizures by disconnecting the cross-communication of neurons.
Stereotactic radiosurgery involves the delivery of a focused beam of radiation to a specific target area. Gamma Knife radiosurgery, one of the most common forms of radiosurgery, uses gamma rays to target the area to be treated. In epilepsy, it is generally reserved for small, deep-seated lesions that are visible on MR imaging.
There are currently two FDA-approved devices that modulate the nervous system with the goal of improved seizure control. This includes vagus nerve stimulation and responsive neurostimulation. Both devices are considered palliative in that the goal is improved seizure control, and rarely do patients become seizure free.
Vagus nerve stimulation
The vagus nerve stimulator (VNS) is an FDA-approved device for the treatment of epilepsy that is not controlled with antiepileptic medications. It involves the surgical placement of electrodes around the vagus nerve in the neck and a generator placed below the collar bone in the upper chest region. It requires two separate incisions, but is an outpatient procedure. Subsequently, a programmer can be used by the epileptologist (from outside the skin) to change the intensity, duration and frequency of stimulation to optimize seizure control. VNS decreases seizure frequency by at least half in 40 to 50 percent of patients, but rarely eliminates all seizures. It is an option for those who are not candidates for other types of surgery.
Responsive neurostimulation (RNS)
The NeuroPace responsive neurostimulation (RNS) device was approved by the FDA in 2014 as a treatment for adults with partial-onset seizures with one or two seizure onset-zones, whose seizures have not been controlled with two or more antiepileptic drugs. Surgery involves placing a neurostimulator in the skull and connecting to two electrodes that are placed either on the surface or into the brain, in or around the area which is deemed to be the likely onset region for the seizure. The device records brain waves (EEG), and is trained by the epileptologist to detect the electrical signature of the seizure onset and then deliver an impulse which can stop the seizure. Data collected by the neurostimulator can by uploaded by the patient with the use of a hand-held wand to a secure web-based application which can be accessed by the epileptologist. This surgery is generally reserved for patients who are not a candidate for surgical resection, since the RNS improves seizure control but rarely stops seizures from occurring.
Improved technology and testing has made it possible to identify more accurately where seizures originate in the brain (epileptogenic regions), and advances in surgery have made operative management safer for all forms of surgery for epilepsy. Of the surgeries presented, surgical resection offers the best chance of rendering a patient seizure-free. However, the benefits of surgery should always be weighed carefully against its potential risks.
Living and Coping with Epilepsy
People with epilepsy are at risk for two life-threatening conditions: tonic-clonic status epilepticus and sudden unexplained death in epilepsy (SUDEP). Tonic-clonic status epilepticus is a long-lasting seizure that’s considered a medical emergency. If not stopped within about 30 minutes, it may cause permanent injury or death.
SUDEP is a rare condition in which young or middle-aged people with epilepsy die without a clear cause. It accounts for less than two percent of deaths among people with epilepsy. The risk is about one in 3,000 per year for all people with epilepsy. However, it can be as high as one in 300 for those who have frequent, uncontrollable seizures and take high doses of seizure medicines. Researchers are uncertain why SUDEP causes death. Some believe that a seizure causes an irregular heart rhythm. More recent studies have suggested that the person may suffocate from impaired breathing, fluid in the lungs and lying face down on bedding.
Although the risk is low, people with epilepsy also can die from inhaling vomit during or just after a seizure.
Most women with epilepsy can become pregnant, but they should discuss their epilepsy and the medications they are taking with their doctors before getting pregnant. Many patients with epilepsy take high doses of medication that may lead to potentially harmful drug exposure to unborn babies. In some cases, medications may be reduced before pregnancy, particularly if seizures are well-controlled. While seizure medications can produce birth defects, severe birth defects are rare in infants of women who receive regular prenatal care and whose seizures are carefully managed. Women with epilepsy have a 90 percent or better chance of having a normal, healthy baby.
Epilepsy is a chronic condition that affects people in different ways. Many people with epilepsy lead normal, active lives. Between 70 and 80 percent of people with epilepsy can successfully control their seizures through medication or surgical techniques.
Some people find that they rarely have to think about epilepsy, except when taking their medications or going to see the doctor. No matter how epilepsy affects a person, it is important to remember that being well-informed about the condition and keeping a positive attitude are important. Working closely with ahealthcare team and adhering to prescribed medications are essential to helping control seizures so that the patient can lead a full, balanced life.