The Role of Nonpharmaceutic Conservative Interventions in the Treatment and Secondary Prevention of Epilepsy
Address correspondence and reprint requests to Prof. Dr. P. Wolf at Epilepsie-Zentrum Bethel, Klinik Mara 1, Maraweg 21, D-66317, Bielfeld/Germany. E-mail: firstname.lastname@example.org
Summary: Nonpharmacologic conservative treatments receive too little attention. Depending on the clinical condition of the patients, they may be used alone or in conjunction with other therapies. Their target is the single seizure rather than the epileptic condition as such. They belong mainly to one of three domains.
Nonspecific prevention of seizures: The first step is the identification of factors facilitating the occurrence of seizures. In the second step, strategies to control these factors are developed. Most common are disturbances of the sleep–wake cycle, especially reduction of sleep. Patients should follow a regular sleep schedule with deviations of not >2 h. Sometimes a sleep calendar is helpful. Night shifts are not compatible with seizure prevention in these cases. Sleep disturbances as a facilitating factor of seizures are particularly common in juvenile idiopathic generalized epilepsies, in which their avoidance is in many cases an indispensable part of the therapeutic regimen, along with appropriate drug treatment. They are the most common precipitating factor in adolescents and adults with a first epileptic [mostly generalized tonic–clonic (GTC)] seizure. In these instances, their avoidance is central to the secondary prevention of epilepsy developing from the single seizure, whereas the prescription of antiepileptic drugs (AEDs) is rarely effective. Other nonspecific facilitators of seizures include uncontrolled use of alcohol and extraordinary stress. Patients must learn how to cope with stressful events.
Specific prevention of seizures: In reflex epilepsies, specific precipitants of seizures are the targets of interventions. Thus, most patients with primary reading epilepsy begin to have, with prolonged reading, perioral reflex myoclonias, which enable them to stop reading and thus to avoid a GTC seizure. In photosensitive patients, seizures are often precipitated by television. These can be avoided by viewing from a distance and using a remote control, small screens in a well-lit room, and preferably with a 100-Hz line shift. Environmental flicker stimulation often comes unexpectedly, and it is advisable that the patients always wear sunglasses in brightly lighted surroundings. Polarized glasses seem to be more protective than plain sunglasses. If the patient has only photically induced seizures, treatment by specific prevention alone may be sufficient, but if spontaneous seizures also occur, drugs must be given in addition.
Arrest of seizures: Focal seizures that develop sufficiently slowly to leave the patient time to react may be interrupted by “countermeasures.” These, again, may be nonspecific (acting by relaxation, concentration, or a combination of both) or specific. The latter are individually tailored, based either on spontaneous experiences of the patient or on the anatomy of ictogenesis. Seizure propagation is blocked when a major part of the neurons involved is activated and not recruitable for spread of the epileptic discharge. Seizure arrest rarely is used alone but usually in combination with partially successful pharmacotherapy.
From the perspective of modern epileptology, in which we have many pharmaceutic and surgical interventions but still are concerned about therapy resistance, it is surprising that, in the ages-old history of epilepsy (1), this condition has never been considered untreatable. Thus, the author of the 2,400-year-old text, “On the Sacred Disease,” ascribed to Hippocrates, states that epilepsy becomes incurable only if it lasts too long. When we ask how this ancient Greek physician may have treated epilepsy, we learn that, as in all illness, one had to apply the element that was inimical, and not what was favorable and habitual to it. This also is the principle of the treatments discussed here.
In the time of Galen, the second century AD, the method known to interrupt a focal motor seizure starting in the periphery of a limb was the application of a proximal ligature. Gowers (2) wrote extensively about treatment by seizure “arrest,” and developed theories about its mode of action. From case reports of the late nineteenth century [e.g., Horsley's reports (3) of what can be considered the first cases of epilepsy surgery], it becomes apparent that, in that period, a case history would have been considered incomplete if it had not included data about such treatments and their effect.
After that, it seems that this part of epilepsy therapeutics was rapidly forgotten, probably in consequence of the progress made in drug treatment. The recently renewed interest in these treatments (4–6) probably has several causes: the recognition that despite the newest drugs and the progress of epilepsy surgery, some patients go on to have seizures; the decreasing willingness of a whole generation to rely on “chemistry,” which they perceive as unnatural; an increasing interest in patients' experiences, especially their perception of loss of control by the seizures, which is counteracted by the particular element of self-control that is common to these treatments; and last but not least, the perpetual challenge of discovering additional therapeutic routes.
Nonpharmaceutic conservative (NPC) treatments for epilepsy can be used alone or in conjunction with other therapies (7,8). Their target is the single seizure rather than the epileptic condition. This makes some of them especially adequate for the secondary prevention of epilepsy after a first and single seizure. They belong mainly to one of three domains (i.e., nonspecific and specific prevention of seizures, and arrest of seizures).
NONSPECIFIC PREVENTION OF SEIZURES
Here the first step is the identification of factors facilitating the occurrence of seizures. In a second step, strategies to control these factors are developed. Disturbances of the sleep–wake cycle, excessive alcohol intake, and sometimes extraordinary physical and psychic stress are among the well-known factors that increase the likelihood of having seizures in many patients, especially among those with idiopathic generalized epilepsies. Likewise, they are the most common precipitating factors of a first epileptic (usually generalized tonic–clonic, GTC) seizure (9). In these cases, their avoidance is central to the secondary prevention of epilepsy after the single seizure, whereas the prescription of antiepileptic drugs (AEDs) is rarely effective.
Most of the facilitating factors can be avoided by a hygienic lifestyle. Thus, patients who have experienced seizure precipitation by disturbances of their sleep–wake cycle should follow a regular sleep schedule with deviations of not >2 h in any direction (shortening or lengthening the total sleep time; sleep at different times). This may have the consequence of a change of workplace to avoid night shifts. If the patient has remained seizure free for 1–2 years, the possible deviations can tentatively be expanded to 3 h, if the patient desires. For those who are used to much more chaotic habits, it may be helpful to keep a “sleep calendar,” in which they note every night when they go to bed and when they get up, together with any possible events. Keeping the calendar helps these patients to keep the discipline.
Absolute abstinence from alcohol rarely is required. A glass of wine or beer with a meal or a glass of champagne at a festive occasion is possible. Hard drinks should be avoided, especially because it is more difficult to control their quantity. If someone is known to have difficulties with stopping after the first glass, we recommend complete abstinence for 1 year, after which a new decision will be made according to the clinical course.
Extraordinary stress often is difficult to avoid, as it may depend largely on conditions outside the control of the patient. However, people can learn, and some need to learn to cope better with and increase their awareness of inadequate responses to stressful events. Thus, in two of my patients, isolated seizures developed repeatedly out of a dramatic increase of their habitual migraines, in response to extraordinary stress. They have learned to understand that an increase of migraine is an indicator of an impending seizure, and to reduce the stress. Both became seizure free without drugs.
SPECIFIC PREVENTION OF SEIZURES
In reflex epilepsies, specific precipitants of seizures are the target of interventions. For example, most patients with primary reading epilepsy have, with prolonged reading, perioral reflex myoclonias, which enable them to stop reading and thus to avoid a GTC seizure (10).
In photosensitive patients (11), seizures are often precipitated by television viewing. These can be avoided by viewing from a distance in a well-lit room, on small screens, preferably with a 100-Hz line shift, and always using remote control. Environmental flicker stimulation often comes unexpectedly, and it is therefore advisable that these patients always wear sunglasses in brightly lit surroundings. Polarizing glasses seem to be more protective than plain sunglasses. It is useful to test a variety of glasses during the EEG investigation with intermittent light stimuli to determine how much light absorption is protective in the individual case.
Typical environmental flicker includes sunshine perceived frontally or obliquely through trees and shrubs, or a glittering water surface. Stroboscopic lights often are used in discotheques, and the patients must be made aware of the risk these carry. In some patients who are very sensitive to flickering lights, even diffuse intermittent lights may be provocative, and such patients should be provided spectacles with lateral shields.
If for some reason a patient is exposed to flickering lights without protection, he or she should be advised to cover one eye completely with the palm of the hand.
If patients have only photically induced seizures, treatment by specific prevention alone may be sufficient, but if spontaneous seizures also occur, drugs must be given in addition (8).
Forster (12) described deconditioning methods for many kinds of reflex epilepsies, but few authors have been able to replicate these. Individually tailored approaches are typically required in these instances, as in a patient with tonic versive seizures precipitated by touch, in whom we could significantly reduce the seizures by a deconditioning program (13).
ARREST OF SEIZURES
Focal seizures that develop sufficiently slowly to leave the patient time to react may be interrupted by “countermeasures.” These again may be nonspecific or specific.
Nonspecific seizure arrest uses relaxation, concentration, or combinations of both. Patients may concentrate on certain thoughts or phrases, mental calculations, or images. They also may focus their attention on something in their environment or visual field. In most cases, however, it is important to exclude the element of chance and to train with a certain method that is always used.
With respect to relaxation, for some patients, it is sufficient to breathe quietly and concentratedly. Others may learn specific relaxation methods such as progressive muscle relaxation or autogenous training. The use of yoga for epilepsy was recently reviewed by Yardi (14). Of the various methods of EEG biofeedback that have been applied in epilepsy, the most successful seems to be the one producing a positive shift of the cortical DC potential (15).
Specific seizure arrest must be tailored individually. It consists in the activation, by some sensory or cognitive input, of a cortical area close to the seizure-onset zone, and which is involved in the patient's habitual seizure spread. The rationale of this intervention is that the generation of paroxysmal depolarization shifts requires an intermediate state of activation of the neurons. The stimulations used for specific seizure arrest result in depolarization of sizable neuron pools. As long as the depolarization lasts, these neurons are not recruitable for the spread of the epileptic discharge, and the seizure is arrested by the blockade of its further propagation.
The methods used may be based on the patient's spontaneous experiences with seizure interruption. Various studies have shown that close to 60% of patients with focal seizures have such experiences (16,17). If this is not the case, the interventions proposed must relate to the anatomy of the patient's seizure development as it appears from a detailed analysis of the sequence of seizure signs and symptoms.
Thus, the proximal ligature used to arrest focal motor seizures activates the sensorimotor cortex. It must be tight to produce a strong effect, and “if the commencing fit has got beyond the part to which the ligature is applied, the attack is not arrested”(2). In the famous case of Efron (18), an olfactory hallucination habitually appeared at a relatively late stage of a lengthy aura development, and the interruptive stimulus used was a smell from a sniff bottle that was applied in the stage immediately preceding the hallucination. This patient was treated without drugs and, with systematic application of seizure arrest, eventually reached a complete cure from her seizures.
Seizure arrest is rarely used alone but usually in combination with partially successful pharmacotherapy. To become therapeutically effective beyond the occasional interruption of a seizure that many patients experience, it must be applied systematically and with optimal timing, for every commencing seizure. It also is highly recommended to let the patients train with their method of interruption, if possible several times a day, imagining the aura and then applying the countermeasure.
One of our patients (6; case 3) had simple focal tonic seizures with possible secondary generalization. They commenced with paresthesias in the left hand, which he could abort by clenching his fist. He was counseled to use this countermeasure always, at the very onset of the paresthesias, and exercise the procedure several times every day by imagining the aura and clenching his fist. For 6 months, he did not follow the advice and went on to have seizures as before. When he complied with a repetition of this instruction, a dramatic decrease in seizure frequency occurred over a period of 6 months, after which the seizures completely disappeared. He reported that he did not consciously apply the arresting method any longer but frequently caught himself having clenched his left fist without paying attention to it.
Usually epilepsy therapy, both pharmacologic and surgical, aims at complete seizure control, if possible including isolated auras. Ongoing isolated auras indicate that the epilepsy is still active. Seizure arrest is a strategy that requires the occurrence of auras, as otherwise, it cannot be applied. The optimal expected outcome of this approach is that the patients have only isolated auras. One of the most surprising and still unexplained features of this treatment is that it may end with complete disappearance of seizures. The repetitive interruption of seizure activity by a dynamic procedure seems thus to have a different effect from those produced by AEDs, or from the removal of epileptogenic tissue by neurosurgery.
An eventually curative effect of seizure arrest has been observed only in patients in whom, beyond the detection of an effective countermeasure and its systematic well-timed application with successful arrest of all seizures, the consciously applied countermeasure became replaced by a conditioned response in which the aura triggered the interruptive response without the patient's volitional reaction (as in the case just mentioned; 6). The next step, in which the seizure activity may fade away, is still not fully understood. The conditioned response also has hitherto always developed spontaneously. This therapy could perhaps become still more useful if methods were developed to facilitate the conditioning of the response.