How does epilepsy occur?
The brain is the organ that governs human consciousness, thinking, emotion, movement and receiving various sensations. The physiological functions of the brain are realized through bioelectrical activities, and bioelectrical phenomena and excitability of cells are one of the basic functions of cells, and various life activities of human beings are inseparable from bioelectrical effects.
From the previous definition of epilepsy, we know that epilepsy is caused by excessive synchronous abnormal discharge of neurons in the brain. Under normal conditions, the body keeps the neurons in the brain in a relative balance of excitation and inhibition through its own regulatory mechanism, and the discharge of nerve cells is maintained within the physiological range (1-20Hz).
When neurons in a certain part of the brain undergo degeneration, necrosis, absence, structural abnormalities, etc., the neurotransmitters of neurons change (excitatory transmitters increase or inhibitory transmitters decrease) and the distribution ratio of ions (mainly potassium and sodium ions) inside and outside the cells changes, causing a large number of neurons in the brain to discharge excessively synchronously, and the frequency can reach hundreds to thousands of Hz, which causes clinical epilepsy. This causes clinical seizures.
The pathogenesis of epilepsy is a complex issue that involves the intrinsic nature of the nervous system, the imbalance between excitatory and inhibitory processes, the starting point of seizures (epileptic foci), and the generation, propagation, and termination of epileptic waves. Although many findings have been made, the exact mechanisms have not been elucidated.
1. Generation of epileptiform activity.
Local structural changes in the brain and imbalance of the local internal environment can be caused by the action of brain damage factors. Genetic factors make certain parts of the brain have higher susceptibility to brain damage factors such as unstable neuronal membrane potential or lowered convulsive threshold. Under the combined effect of both pathogenic factors, the local neuronal membrane potential activity is abnormal and the balance between excitatory and inhibitory activity is imbalanced.
It has been shown that neurons in the epileptic focal zone have increased excitability and are in a constant state of partial depolarization and paroxysmal depolarization drift, and this membrane potential abnormality may be related to the transmembrane movement of calcium ions.
Due to the altered (increased) permeability of the cell membrane to ions, neurons are prone to be activated and excitability is increased under conditions such as mild elevated body temperature, hypoglycemia, hypocalcemia, hyponatremia, and sensory stimuli (e.g., flashing lights) and a certain timing of sleep. When the excitatory activity increases and the inhibitory activity decreases to a certain threshold (convulsive threshold), the neurons further depolarize and burst discharges occur, and epileptic waves can be recorded on the EEG. Due to the activation of the feedback inhibition pathway, the epileptic waves are confined to the epileptic focus and cannot spread to the periphery or contralateral side, and there is no clinical manifestation of seizures.
In the absence of clinical seizures, epileptiform wave activity is confined to the periphery and/or the contralateral side of the focal area due to the activation of the feedback inhibitory pathway, which can be substantially increased and/or significantly decreased or completely eliminated by some promotive factors (internal or external environmental factors). The exact mechanism that regulates the conversion of interictal epileptiform activity to diffusible epileptiform activity during seizures is not fully understood and may be related to spontaneous firing or synchronous afferent bursts in the central neuronal starting point.
Subtle changes in the transmembrane movements of various ions and multiple neurotransmitter systems occur in the generation, spreading, and termination of the membrane potential and epileptic focal neurons, such as elevated extracellular potassium ions in the epileptic focal area, defective cell membrane voltage-sensitive calcium channels, significantly reduced inhibitory neurotransmitter γ-aminobutyric acid (GABA), 5 GABA (GABA), 5-HT (5-hydroxytryptamine), and glycine are also decreased, excitatory neurotransmitters glutamate and acetylcholine are increased or decreased, and the neuromodulator taurine is increased. However, the causal relationship between these biochemical changes and epileptic seizures is controversial.
2. Propagation of epileptic activity.
The propagation of epileptic activity is related to the etiology, location and number of epileptic foci, as well as the neural network system (circuit) and the feedback inhibition triggered by epileptic activity.
When epileptiform activity spreads locally from the epileptic focus to adjacent brain regions and no longer spreads, the clinical presentation is a partial seizure. In addition to feedback inhibition of the lateral branches of the neuronal axons, the mechanism that prevents the spread of epileptic waves is also related to extra-cortical (cerebellar and other extrapyramidal) inhibition, which can spread to the thalamus and midbrain reticular formation when the inhibition is insufficient, causing loss of consciousness, and then spread to the entire cerebral cortex via the thalamic projection system, resulting in generalized tonic clonic seizures. Occasionally epileptiform activity operates within the cortical synaptic ring for prolonged periods (hours to months),’ and partial epileptiform persistence occurs.
The clinical manifestations of partial seizures are complex and varied due to the location of the epileptic focus and the route and extent of propagation of epileptic activity. Epileptiform activity originating in the midbrain and thalamus spreads to the bilateral cerebral cortex via the thalamic projection system and manifests as primary grand mal seizures. The absence of seizures is thought to be caused by the involvement of deep midline structures (bilateral paraventricular nuclei of the thalamus, rhombomere nuclei, inner plate nuclei, and lateral rigid nuclei of the superior colliculus), as far as the connections between the various nuclei at these sites and between them and the cerebral cortex have not been clarified. Infantile spasms may be related to imbalance in the regulatory mechanisms of the brainstem (brain bridge).
3. Termination of epileptiform activity.
The termination of epileptic seizures depends on various levels of inhibition and has little relationship with the energy consumption of neurons, including.
(1) the role of inhibitory neurons (GABAergic neurons) around the epileptogenic focus.
(2) uptake of excitatory substances by glial cells.
(3) Inhibitory effects in the substantia nigra, caudate nucleus, and cerebellum.
(4) Some substances released from the brain during epileptic activity, such as beta-endorphin, adenosine, hypoxanthine, creatinine, and cholecystokinin, also have a role.