Epilepsy: causes

Causes of epileptic seizures

Any damage to the brain may be the cause of the formation of an epileptic focus, but more than half of patients with epilepsy do not show any focal lesions or any other obvious causes. It is assumed that in such cases there is a latent (microstructural) damage or imbalance of the exciting and inhibitory neurotransmitter systems in the brain. Specialist epileptologists currently distinguish two types of epilepsy:

1. idiopathic, that is, not associated with any focal damage and allegedly of a hereditary nature;
2. cryptogenic, that is, epilepsy, caused by a specific lesion of a non-genetic nature, which in the future can in principle be established.

With age, the specific gravity of these or other causes of epileptic seizures is changing. In childhood, seizures are especially often caused by birth trauma, infections (eg, meningitis) or fever. In middle age, seizures are more often associated with craniocerebral trauma, infections, with the use of alcohol, cocaine or medicines. In the elderly, the most common causes of seizures are brain tumors and strokes. However, at any age, seizures associated with cryptogenic epilepsy are most common.

[1], [2], [3]

Genetic causes of epileptic seizures

Fundamental scientific and clinical studies have made it possible to establish the importance of genetic factors in the origin of epilepsy. Genetic factors are particularly important in generalized forms of epilepsy, manifested by absences, generalized tonic-clonic seizures, or myoclonic seizures. Apparently, the genetic defect does not in itself cause epilepsy, but rather changes the sensitivity of the brain, as a result of which a person becomes predisposed to the development of epilepsy. Sometimes for the development of epilepsy, it is necessary to combine several genetic changes or a combination of a genetic defect with external factors. Over time, many, perhaps hundreds, of genetic mutations associated with the development of epilepsy will be discovered. Although relatively few such genetic mutations have now been established, it is one of the fastest growing areas of research. Once it is possible to better characterize the genetic predisposition to seizures, pharmacological companies will have the opportunity to develop new, more effective and safe antiepileptic drugs.

Relatives of patients with idiopathic forms of epilepsy have a higher risk of epileptic seizures, compared to other individuals. But since the penetrance of genes predetermining the development of epilepsy is rather low, most relatives do not have this disease. Some forms of epilepsy caused by focal lesions of the brain are not of a genetic nature, nevertheless may be associated with a genetically determined predisposition, which, for example, increases the likelihood of developing seizures after a traumatic brain injury.

Craniocerebral injury

The prevalence of craniocerebral trauma (TBI) in recent decades is growing like an epidemic. Craniocerebral trauma is one of the main causes of epilepsy. Nevertheless, most people who have suffered a brain injury do not develop epilepsy, because in order to cause epilepsy, the traumatic brain injury must be severe enough and cause irreversible damage to the brain. Usually epilepsy occurs after a penetrating brain injury or a severe closed trauma that causes a prolonged coma and amnesia. Concussion, usually accompanied by a short-term loss of consciousness, usually does not lead to the development of epilepsy. The onset of seizures at the time of injury does not mean that epilepsy will necessarily develop later on. In such cases, antiepileptic drugs should be prescribed only for a short period, and later they can be subjected to a trial cancellation to assess the need for their further administration. Post-traumatic epilepsy may occur several years after the injury. Special algorithms have been developed to predict the likelihood of epilepsy following a traumatic brain injury.

[4], [5], [6], [7], [8], [9], [10]

Tumors of the brain

Tumors of the brain are a very serious, although relatively rare, cause of epileptic seizures. Epileptic seizures can cause both benign and malignant tumors, including meningiomas, benign or malignant astrocytomas, glioblastomas, oligodendrogliomas, gangliongliomas, lymphomas and local tumors. Seizures caused by a tumor usually have a focal (partial) character, and their manifestations depend on the localization of the tumor. With some exceptions, for example, with ganglioglio, seizures are usually not generated by the cells of the tumor itself, but by the surrounding tissue, irritated by the tumor. Focal seizures caused by a brain tumor are difficult to treat. Sometimes the only realistic goal of treatment is the blocking of secondary generalization. With successful treatment of a tumor, seizures usually shrink and become less pronounced. Patients should be warned that complete or partial removal of the tumor by surgery, radiation or chemotherapy does not always lead to a complete regression of epileptic seizures. In this regard, the need for antiepileptic therapy can persist for a long time. In a patient with a brain tumor, an inexplicable change in the frequency or nature of seizures always requires an additional examination.

Infections

Epileptic seizures in children and adults are relatively often caused by infectious diseases, especially bacterial, fungal or viral meningitis. Seizures occur also with direct damage to brain matter in encephalitis or abscesses. All these infections can be manifested by repeated seizures. With encephalitis caused by the herpes simplex virus, which usually affects the temporal lobe, the likelihood of epileptic seizures is especially high. Across the world, parasitic infestations (eg, cysticercosis) are one of the common causes of epilepsy. In recent years, the importance of toxoplasmosis as a cause of seizures in patients with AIDS has increased.

Stroke

In that part of the brain, where a partial damage occurs in stroke, but not cell death, an epileptic focus can form. Approximately in 5-15% of cases, seizures occur in the acute phase of stroke (more often with embolic and hemorrhagic strokes), but later only less than half of these patients develop persistent epilepsy. Seizures caused by stroke are usually focal or secondary generalized. Sometimes vascular lesions of the brain are not clinically apparent due to the small size of the focus or its localization in the functionally mute zone. Minor strokes may not be remembered by patients and not visualized with MRI. Often a patient with newly developed seizures is suspected of a small stroke, but it is not possible to confirm this assumption or to determine the location of the focus with the help of neuroimaging. The reverse problem arises in elderly patients with newly developed seizures, in which MRI almost always reveals diffuse or fine-focal changes in white matter associated with damage to small cerebral vessels. At present, it is not possible to determine whether seizures are associated with these microinfarctions or not.

Epileptic seizures caused by dysplasia

Dysplasia is the accumulation of normal brain cells in an unusual area of the brain for these cells. To denote dysplasia, the terms "migration irregularities", "heterotopies", "developmental anomalies" are also used. The signals, through which the developing neurons migrate to the proper areas of the brain, are poorly understood. Perhaps some brain cells receive incorrect "instructions" and in the process of migration overcome only part of the way to the cortex. Perhaps, because these cells are not surrounded by their usual neighbors, they escape from control, which normally inhibits their excitability. Dysplasia occurs more often than previously thought. Although they are usually invisible in computed tomography, they can be identified with high-resolution magnetic resonance imaging. The severity of dysplasia varies from invisible in MRI microsplasia to an expanded dysplastic syndrome, for example, in tuberous sclerosis.

[11], [12], [13], [14], [15], [16]

Biochemical imbalance

Not always seizures occur as a result of structural damage to the brain. Biochemical imbalances can cause seizures in cases where the MRI does not reveal any changes. Biochemical equilibrium in the brain can disrupt a variety of substances or pathological factors, including alcohol, cocaine, psychostimulants, antihistamines, ciprofloxacin, metronidazole, aminophylline, phenothiazines, tricyclic antidepressants, hypoglycemia, hypoxia, hyponatremia, hypocalcemia, renal or hepatic insufficiency, complicated pregnancy.

[17], [18], [19]

Hormones

Some women note the relationship between the development of seizures and the menstrual cycle. In addition, during pregnancy, there can be both an increase in frequency and a decrease in seizures. Seizures sometimes occur or occur more severely during puberty and can be smoothed out during menopause. Female sex hormones, especially estrogens and related compounds, are able to regulate the excitability of the brain, which explains the relationship between hormones and epileptic seizures. Unfortunately, there is as yet no way to influence the hormonal balance in such a way as to provide long-term control over seizures.

Situations provoking epileptic seizures

Although most seizures occur spontaneously, there are certain factors that can provoke their occurrence. These include skipping reception of antiepileptic drugs, certain phases of the menstrual cycle, pregnancy, flashing lights, watching TV, video games, lack of sleep, intercurrent illness, migraine. Rarely, provoking factors are certain sounds, food, sensory stimuli, changes in temperature. Although stress is also often called as a provoking factor, this relationship is not proven. In our society, stressful situations are very common, but in their majority they do not provoke the development of seizures. In this regard, it remains unclear why in some cases, stressful situations provoke seizures, and in others - not.

Alcohol use and alcohol abstinence are often triggering factors of seizures, as well as a sudden stopping of sedatives and hypnotics, for example, barbiturates or benzodiazepines. Many commonly used drugs can cause epileptic seizures, but there is no evidence that caffeine or smoking can provoke seizures, although some patients note individual sensitivity to these substances. There are reports of extremely unusual provoking factors, for example, in some patients seizures are caused by certain smells, sounds of music and even thoughts. Some factors are mistakenly considered provocative because of coincidence. This possibility is more likely in the event that the seizure occurs more than a day after the impact of the alleged provoking factor, or if the seizure only once appeared after the influence of a particular factor. In fact, most seizures occur without any provoking factors.