Epilepsy: causes and treatment

Causes and symptoms of epilepsy

Epilepsy is considered a functional brain disorder, which manifests itself in the form of seizures, during which neurons produce sudden and short-time uncontrolled impulses.

The causes of epilepsy are varied: congenital or acquired abnormal changes in the brain; metabolic disorders (diabetes, thyroid disease, etc.); genetic mutations, including hereditary ones. Combined, genetic and structural-metabolic cases of epilepsy are also known: the symptoms of an inherited disease appear only as a result of a significant trigger – a stroke, meningitis, poisoning, etc. In some cases, the cause cannot be established, so they are referred to as idiopathic.

The main symptoms of epilepsy

The main signs of epileptic seizures are well-known and include a fixed gaze, hypertonia, loss of consciousness, rhythmic, sometimes asynchronous convulsions, wheezing, biting the tongue. The attack ends with drowsiness and mental confusion. Such episodes often occur upon awakening, and last no longer than 90 seconds (they should not be mixed up with psychogenic seizures which can last for several minutes). Still, not every physician can make the correct diagnosis of epilepsy. The reasons include the variety of the disease forms, as well as of the intensity and frequency of symptoms. When an attack occurs, it is important to get the advice of a competent specialist as soon as possible. First, the expert will be able to distinguish the true symptoms from signs of other disorders with similar manifestations. These can be cerebrovascular events, drug or heavy metal poisoning, meningitis, concussions, or metabolic disorders. Second, the fastest possible examination does not only ensure a correct diagnosis, but also increases the treatment effect.

The Importance of the Anamnesis in Diagnosis-Making

The correct diagnosis largely depends on comprehensive anamnesis taking. The highest risk of an epileptic seizure hides itself behind previous manifestations: the probability of relapse increases to 70% after two unprovoked episodes without convulsive symptoms. It is important not to miss "harmless" cases. The most typical causes of misinterpretation are panic attacks or behavioral disorders that are not associated with epilepsy. However, generalized motor manifestations may be underestimated.

The most common (11-50%) diagnostic errors occur in patients with psychogenic non-epileptic seizures. Often the mistake is revealed when patients report a long-term lack of effect from taking antiepileptic drugs. Although experts are well aware of a number of significant differences:

- after an epileptic attack the patient is lethargic, almost non-responding to stimuli, while in a state of psychosis the patient can start speaking a foreign language or imagine living at a different age;

- in contrast to psychogenic ones, true epileptic seizures are characterized by slow head movements to the sides.

Patients with resistance to antiepileptic drugs should contact specialized centers, as the consequences of improper treatment can be extremely severe. Mortality in such patients is statistically 2.5 times higher than in those receiving the correct treatment.

What exams should be done to confirm epilepsy?

In addition to a case history, special tests and imaging studies are necessary. They allow to identify possible abnormal changes.

Electroencephalography in the diagnosis of epilepsy

Electroencephalography (EEG) is recommended to be performed within half an hour after the attack, at the latest within 24 hours. According to most experts, the presence of epileptic potentials is most reliably recorded during this period.

A study involving 170 patients, completed in Germany in 2020, indicates that the most reliable EEG results were obtained within the first 16 hours. This allows to decide on the appropriateness of antiepileptic drugs.

In daily practice, the correct interpretation of EEG findings is of key importance.

Incorrect assessment of normal variants based on EEG results can lead to misdiagnosis and, subsequently, to incorrect treatment. In particular, the so-called Wicket spikes, which are similar to the epileptic potentials of temporal lobar epilepsy with symptoms of drowsiness, should be considered as variants of normal.

Video monitoring as an important study option

For a more comprehensive examination, a 1-3 day EEG with video recording is performed. A video of the patient taken at the time of the attack can significantly help in the correct diagnosis. Only an experienced epileptologist can interpret such data correctly.

Epilepsy MRI scans

Timely performed MR imaging in conjunction with EEG makes it possible to confirm the presence of structural abnormalities. In such cases, the probability of recurrence exceeds 60%. If there are no structural changes, the risk of recurrence is significantly lower, namely, from 19 to 26%.

Treatment prospects

Epilepsy is not curable. The goal of therapy is to reduce the frequency and intensity of seizures as much as possible. Some patients can experience single episodes of the disease that do not require treatment.

The first-line therapy involves medications. If it is ineffective, surgery can be considered.

Drug treatment

Recurrent seizures require therapy with anticonvulsants. The regimens should be determined by specialized health care facilities, where the drug type and dosage can be selected carefully, taking into consideration a whole range of factors. One of the most important ones is drug tolerance.

However, the best results are often achieved by a combination of several medications. Only a highly qualified specialist with appropriate expertise can suggest an effective treatment regimen and determine the treatment duration. In certain cases, therapy can be lifelong.

When prescribing antiepileptic drugs, the following factors are taken into account:

     • physical condition, weight and cognitive abilities;

     • personal life goals, such as the desire to have a child;

     • comorbidities and medications taken to manage them.

Neurostimulation

If medicines fail to prevent epilepsy attacks, neurostimulation may be used. This method is not exactly perfect, since it does not guarantee complete suppression of epileptic activity either, but it may bring some improvement. The most common procedure types are:

Vagus nerve stimulation. The method uses a pacemaker implanted subcutaneously in the collarbone area and connected to an electrode that is attached to the vagus nerve area in the neck. The device generates regular electrical impulses to suppress seizures.

Deep brain stimulation also involves electrical impulses, but in this case, they are generated by electrodes implanted in certain brain areas. The aim is the same, that is, the suppression of epileptic activity.

Antiepileptic surgery

If conservative therapy fails, the remaining option is surgery. As a rule, it is performed if the condition is associated with focal brain lesions, since with a generalized form it is impossible to identify abnormal areas to be removed. Indications for surgical treatment are determined by epileptologists together with neurosurgeons and radiologists. Decision-making involves the assessment of surgical risks; in particular, the chances that intervention may result in partial or complete loss of speech, mental activity, and other functions.

There are two types of epilepsy operations:

     • resective (with curative effect): the seizure-initiating zones are removed completely, eliminating the disease cause. Preliminary testing is carried out to assess the possible consequences of lesion resection. For example, if the temporal area is affected, doctors evaluate the chances to spare the memory function.

     • Non-resective (palliative) operations do not result in complete relief from seizures. Such interventions prevent frequent and severe attacks and help reduce the use of anticonvulsant medications. The goal is not to remove a lesion, but to cut the connections between brain areas, which interrupts the transmission of an attack provoking impulse.

Laser ablation

A minimally invasive alternative to open surgical resection is laser interstitial thermal therapy (LITT), which uses laser-generated heat to remove foci of epilepsy.

Surgeons implant a laser probe precisely into the center of the epileptic lesion through a small hole. The probe then delivers energy to raise the temperature in a controlled manner and precisely destroy the affected area of the brain, which is called ablation. Temperature measurement allows the progress of treatment to be monitored on the MRI in real time.

In order to use LITT in patients with drug-resistant epilepsy, the epileptogenic area must be clearly defined and small in size.

This method carries a lower risk of cognitive side effects and is particularly preferable for deep foci. With proper candidate choice, this technique can significantly improve seizure control and quality of life, as well as reduce the dose of antiepileptic drugs.

Laser ablation for epilepsy is a relatively new technique, for example, in Europe it was approved in 2018. As experience is gained, the list of possible target structures for the ablation procedure is constantly expanding.

Focused ultrasound: a promising non-invasive therapy

A new and rapidly developing treatment for epilepsy is focused ultrasound (FUS). This non-invasive procedure uses high-intensity ultrasound beams to selectively target epileptogenic tissue without the need for surgical incisions. Initial studies have shown the potential of this technique in preclinical models as well as in early clinical applications.

One of the main advantages of ultrasound is its gentle nature. It eliminates the need for incisions and thus the risk of infection, complications and long recovery.

Clinical studies have shown that FUS can effectively reduce seizure frequency in patients with drug-resistant epilepsy, especially when applied to well localized foci. Another significant advantage is the ability to preserve cognitive abilities, making this technology a suitable treatment option for patients with epileptogenic foci near the areas of the brain responsible for speech.

Scientific Research Perspectives

The University of Bern Department for Diagnostic and Interventional Neuroradiology in Switzerland is currently investigating possible areas of functional brain damage in patients with primary unprovoked seizures. The purpose of the study was to identify biological markers of epilepsy. Experts proceed from the fact that brain areas with the same structure may be functionally interconnected.

In particular, one of the studies revealed that in patients with the temporomandibular form of the disease, the fixed structural relationships in the EEG, which did not detect abnormality, differed from the EEG of healthy patients. The research team was able to use MRI to determine which hemisphere of the brain was affected.

Thus, the study of such relationships gives a chance to identify biomarkers relevant both for diagnosis and classification of epilepsy.

References:

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8. Image source: Free Stock photos by Vecteezy