Epilepsy - Causes

Causes of epileptic seizures

Any damage to the brain can be the cause of the formation of an epileptic focus, but in more than half of patients with epilepsy, no focal damage or any other obvious causes are found. It is assumed that in such cases there is a hidden (microstructural) damage or imbalance of excitatory and inhibitory neurotransmitter systems in the brain. Epileptologists currently distinguish two types of epilepsy:

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

With age, the proportion of certain causes of epileptic seizures changes. In childhood, seizures are especially often caused by birth injuries, infections (such as meningitis), or fever. In middle age, seizures are more often associated with craniocerebral trauma, infections, and the use of alcohol, cocaine, or drugs. 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.

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Genetic causes of epileptic seizures

Basic scientific and clinical research has established the importance of genetic factors in the origin of epilepsy. Genetic factors appear to be particularly important in the generalized forms of epilepsy, which include absences, generalized tonic-clonic seizures, or myoclonic seizures. It appears that the genetic defect does not itself cause epilepsy, but rather alters the sensitivity of the brain, thereby predisposing the individual to develop epilepsy. Sometimes several genetic changes, or a combination of a genetic defect and environmental factors, are needed to cause epilepsy. Over time, many, perhaps hundreds, of genetic mutations associated with epilepsy will be discovered. Although relatively few such genetic mutations have been identified at present, this is one of the fastest growing areas of scientific research. As genetic predisposition to seizures is better characterized, pharmaceutical companies will be able to develop new, more effective, and safer antiepileptic drugs.

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

Traumatic brain injury

Traumatic brain injury (TBI) has been increasing like an epidemic in recent decades. Traumatic brain injury is a major cause of epilepsy. However, most people who have had a TBI do not develop epilepsy because the TBI must be severe enough to cause permanent brain damage to cause epilepsy. Epilepsy usually occurs after a penetrating brain injury or a severe closed head injury that causes prolonged coma and amnesia. Concussion, which usually causes a brief loss of consciousness, does not usually cause epilepsy. Having a seizure at the time of injury does not necessarily mean that epilepsy will develop later. In such cases, antiepileptic drugs should be prescribed for a short period only, and a trial of withdrawal can be performed to assess the need for continued use. Post-traumatic epilepsy may manifest itself several years after the injury. Special algorithms have been developed to predict the likelihood of developing epilepsy after a traumatic brain injury.

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Brain tumors

Brain tumors are a serious, although relatively rare, cause of epileptic seizures. Both benign and malignant tumors can cause seizures, including meningiomas, benign or malignant astrocytomas, glioblastomas, oligodendrogliomas, gangliogliomas, lymphomas, and mestic tumors. Tumor-induced seizures are usually focal (partial) in nature, and their manifestations depend on the tumor location. With some exceptions, such as ganglioglioma, seizures are usually generated not by the tumor cells themselves, but by surrounding tissue irritated by the tumor. Focal seizures caused by brain tumors are difficult to treat. Sometimes the only realistic goal of treatment is to block secondary generalization. With successful tumor treatment, seizures usually become less frequent and less severe. Patients should be warned that complete or partial removal of the tumor by surgery, radiation, or chemotherapy does not always result in complete regression of epileptic seizures. Therefore, the need for antiepileptic therapy may persist for a long time. In a patient with a brain tumor, an unexplained change in the frequency or nature of seizures always requires additional examination.

Infections

Epileptic seizures in children and adults are relatively often caused by infectious diseases, primarily bacterial, fungal or viral meningitis. Seizures also occur with direct damage to the brain tissue in encephalitis or abscesses. All of these infectious lesions can manifest themselves in recurring seizures. In encephalitis caused by the herpes simplex virus, which usually affects the temporal lobe, the likelihood of developing epileptic seizures is especially high. Parasitic infestations (such as cysticercosis) are one of the most common causes of epilepsy worldwide. In recent years, the importance of toxoplasmosis as a cause of seizures in patients with AIDS has increased.

Stroke

An epileptic focus may form in the area of the brain where a stroke causes partial damage but not cell death. Approximately 5-15% of seizures occur in the acute phase of a stroke (more often in embolic and hemorrhagic strokes), but only less than half of these patients subsequently develop persistent epilepsy. Stroke-induced seizures are usually focal or secondarily generalized. Sometimes vascular damage to the brain is not clinically evident due to the small size of the focus or its localization in a functionally silent area. Small strokes may not be remembered by patients and may not be visualized by MRI. Often, a patient with new seizures is suspected of having a small stroke, but it is not possible to confirm this assumption or determine the location of the focus using neuroimaging. The opposite problem occurs in elderly patients with new seizures, in whom MRI almost always reveals diffuse or small focal changes in the white matter associated with damage to small cerebral vessels. At present, there is no way to determine whether the seizures are related to these microinfarcts or not.

Epileptic seizures caused by dysplasia

Dysplasia is a cluster of normal brain cells in an area of the brain that is unusual for these cells. Other terms used to describe dysplasias include migration disorders, heterotopias, and developmental anomalies. The signals that cause developing neurons to migrate to the correct areas of the brain are poorly understood. It is possible that some brain cells receive the wrong instructions and migrate only part of the way to the cortex. Perhaps because these cells are not surrounded by their usual neighbors, they escape the controls that normally inhibit their excitability. Dysplasias are more common than previously thought. Although they are usually invisible on CT scans, they can be detected on high-resolution MRI. Dysplasias range in severity from microdysplasias that are invisible on MRI to a full-blown dysplastic syndrome, such as tuberous sclerosis.

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Disruption of biochemical balance

Not all seizures are caused by structural damage to the brain. Biochemical imbalances may be the cause of seizures in cases where MRI does not reveal any changes. Biochemical imbalance in the brain can be disturbed by a number of substances or pathological factors, including alcohol, cocaine, psychostimulants, antihistamines, ciprofloxacin, metronidazole, aminophylline, phenothiazines, tricyclic antidepressants, hypoglycemia, hypoxia, hyponatremia, hypocalcemia, renal or hepatic failure, complicated pregnancy.

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Hormones

Some women report a connection between the development of seizures and the menstrual cycle. In addition, during pregnancy, seizures may either become more frequent or less frequent. Seizures sometimes occur or become more severe during puberty and may subside during menopause. Female sex hormones, especially estrogens and related compounds, are able to regulate brain excitability, which explains the connection between hormones and epileptic seizures. Unfortunately, there is no way to influence hormonal balance in a way that would provide long-term seizure control.

Situations that provoke epileptic seizures

Although most seizures occur spontaneously, there are certain factors that can trigger them. These include missing doses of antiepileptic medications, certain phases of the menstrual cycle, pregnancy, flashing lights, watching television, playing video games, lack of sleep, intercurrent illness, and migraines. Less common triggers include certain sounds, foods, sensory stimuli, and temperature changes. Although stress is often cited as a trigger, this connection has not been proven. Stressful situations are common in our society, but most do not trigger seizures. Therefore, it is unclear why stressful situations trigger seizures in some cases and not in others.

Alcohol use and alcohol withdrawal are common triggers for seizures, as is sudden withdrawal from sedatives and hypnotics such as barbiturates or benzodiazepines. Many commonly used drugs can cause seizures, but there is no evidence that caffeine or smoking can trigger seizures, although some patients report individual sensitivity to these substances. Very unusual triggers have been reported, with some patients having seizures triggered by certain odors, music, and even thoughts. Some triggers are mistakenly considered triggers because they are coincidental. This possibility is more likely when the seizure occurs more than a day after exposure to the suspected trigger, or when the seizure occurs only once after exposure to the trigger. In fact, most seizures occur without any trigger.