Pathogenesis and neurotransmitter imbalance
Clinical manifestations of the disease directly depend on the precise localization of the activity focus. The patient may experience motor impairments (classic convulsions), autonomic disorders, or psychiatric changes. The administration of pharmacological antiepileptic drugs pursues two main goals: the prevention (prophylaxis) of the onset of seizures or their equivalents, as well as the rapid termination of an ongoing seizure.
The pathogenetic mechanisms of epilepsy development are closely linked to a disruption of the delicate neurotransmitter balance. The formation of persistent epileptogenic activity is rooted in the breakdown of equilibrium between the inhibitory and excitatory systems of the central nervous system.
- Inhibitory systems: normally, activity is suppressed by gamma-aminobutyric acid (GABA) and glycine.
- Excitatory systems: a stimulating effect is exerted by the amino acids glutamate and aspartate.
Biochemical studies show that an abnormally elevated concentration of glutamate is consistently recorded within the established epileptogenic focus. At the same time, the overall GABA content is globally reduced in the brain tissue of epilepsy patients. Excessively released excitatory amino acids actively affect specific neuronal receptors — NMDA and AMPA. Since these receptors are structurally and functionally coupled with fast sodium channels, their activation leads to powerful pathological neuronal excitation.
A genetic factor is also distinguished: there are hereditary forms of epilepsy that are directly caused by polymorphism (structural alteration) of voltage-gated sodium channels.
Generalized seizures
The primary classification of epilepsy forms is based on the extent of pathological electrical activity recorded by electroencephalography (EEG). If epileptiform waves are registered absolutely synchronously in both cerebral hemispheres, such seizures are classified as generalized.
The following main types are distinguished within this group:
- Tonic-clonic seizures (grand mal). Manifest as generalized tonic-clonic convulsions. The seizure is always accompanied by complete loss of consciousness and concludes with a stage of general muscular relaxation. There is a strict danger criterion: if a major seizure lasts more than 5 minutes or seizures follow one another without recovery of consciousness, the condition is regarded as life-threatening status epilepticus.
- Absence seizures (petit mal). The main symptom is a brief loss of consciousness lasting only 5–10 seconds. During an absence seizure, characteristic specific changes are recorded on the EEG.
- Myoclonic epilepsy. This type is characterized by single or serial involuntary twitches of certain muscle groups. Typically, such seizures are short-lived. The main distinction of myoclonic epilepsy is that it proceeds without loss of consciousness.
Partial seizures and status epilepticus
Unlike generalized forms, partial (focal) seizures have a strict localization. According to EEG characteristics, pathological changes during such seizures are limited to a specific area of the brain. Due to the multitude of possible focus locations, the clinical picture of partial seizures encompasses a wide variety of forms. In terms of preservation of consciousness, they are variable: they can occur either with or without loss of consciousness.
A special place in the classification is occupied by status epilepticus. By definition, this is a critical condition in which convulsive seizures follow one another consecutively. Its key feature is that the patient does not regain consciousness in the intervals between seizure episodes.
Briefly: answers to topical questions
What are the main groups of antiepileptic drugs according to their mechanism of action?
Antiepileptic drugs act on several targets: neuronal sodium and calcium channels, GABAergic inhibition, and glutamatergic excitation. The following main groups are distinguished:
- Sodium channel blockers — prevent membrane depolarization; representatives: carbamazepine (Carbamazepinum), phenytoin (Phenytoinum).
- Calcium channel blockers — for example, T-type calcium channel blockers; representative: ethosuximide (Ethosuximidum).
- Agents enhancing GABAergic inhibition — phenobarbital and agents promoting GABA accumulation, such as valproates.
- Agents suppressing glutamatergic excitation — for example, lamotrigine, which suppresses glutamate activity.
Which pharmacological agents are the drugs of choice for the emergency management of status epilepticus?
First-line medications for the emergency termination of seizures in status epilepticus are benzodiazepine derivatives. The drugs are administered intravenously to ensure a rapid effect.
- Diazepam (Diazepamum) is the classic drug of choice for emergency care.
- Lorazepam (Lorazepam) is superior to diazepam in terms of efficacy for terminating status epilepticus.
- Clonazepam (Clonazepam) is also used intravenously to terminate status epilepticus.
Hydantoins (Phenytoin (Phenytoinum)) and general anesthetics or barbiturates (phenobarbital) can be used as additional emergency therapy agents.
How are partial (focal) seizures classified depending on the degree of impairment of consciousness?
Partial (focal) seizures are classified into two main groups depending on whether the patient remains fully conscious during the seizure.
| Seizure type | State of consciousness |
|---|---|
| Simple focal | Consciousness is not impaired |
| Complex focal | Impairment or alteration of consciousness occurs |
Secondary generalized seizures are also distinguished, which begin as focal (with a preceding aura) and then progress to generalized with loss of consciousness.
For quick memorization of neurotransmitter imbalance: "Glutamate Goes (excites), while GABA Guards (inhibits)." In the epileptic focus, there is an excess of what "goes" and a deficit of what "guards".
Class and exam questions
What is an absence seizure (petit mal)?
This is a minor seizure manifested by a brief loss of consciousness lasting 5–10 seconds, accompanied by characteristic EEG changes.
Does the patient lose consciousness in myoclonic epilepsy?
No. Unlike absences and tonic-clonic seizures, myoclonic epilepsy (involuntary twitching of muscle groups) occurs without loss of consciousness.
What is the main danger of status epilepticus?
In status epilepticus, seizures follow one another, and the patient does not regain consciousness between intervals. This condition (as well as a seizure lasting longer than 5 minutes) requires emergency care.
What else to study on this topic
- Mechanisms of action of antiepileptic drugs (enhancement of inhibition, sodium channel blockade)
- Drugs of choice for terminating status epilepticus
- Specific pharmacotherapy for absence seizures (petit mal)
- Drugs for the treatment of partial and generalized seizures
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