Personality changes in epilepsy

Etiology and predisposing factors

The development of the epileptic process is driven by a complex of genetic, organic, and metabolic factors. Hereditary predisposition plays a certain role, but the probability of developing the disease in a child born to completely healthy parents is only about 0.5%.

The morphological picture directly depends on the nature of the seizures. In partial seizures, a local organic scar process can be identified in the brain tissue, acting as an epileptogenic focus. Conversely, in generalized convulsive activity, such structural foci in the brain are not detected.

Of immense importance in triggering the pathological process are metabolic disorders, which act as provoking factors:

• Pathological accumulation of the neurotransmitter acetylcholine in brain tissues.
• A sharp increase in the concentration of sodium ions (Na+) inside neurons.
• Progressive metabolic alkalosis accompanied by the pathological accumulation of ammonia.
• Pronounced vitamin B6 deficiency.

Normally, the central nervous system has its own protective structures. These include the caudate nucleus, the cuneate nucleus, and certain parts of the pons. Their main function is to protect the brain from the generalization of excessive excitation. In epilepsy, a functional or organic weakness of these protective formations is hypothesized.

Neurochemistry and pharmacotherapy principles

The fundamental mechanism of action of modern anticonvulsants is based on eliminating the pathological imbalance between the excitatory and inhibitory neurotransmitter systems of the brain. The main excitatory neurotransmitter is glutamate, and the primary inhibitory one is gamma-aminobutyric acid (GABA).

Regulation of the glutamate system: Agonists of receptors in this system (e.g., kainic acid) are capable of directly provoking seizure states. Antagonists, conversely, demonstrate a pronounced antiepileptic effect. A prominent representative is lamotrigine, which effectively suppresses glutamate activity and physically prevents the excessive influx of Na+ ions into neurons.

Impact on the GABAergic system:

• Barbiturates have a dual action: they reliably block the activity of excitatory glutamate while simultaneously enhancing the inhibitory effects of GABA.
• Anticonvulsants (valproates) disrupt GABA deactivation processes, which contributes to its therapeutic accumulation in brain tissues.

Other neurotransmitters also contribute to the pathogenesis. Glycine and purines (such as adenosine and AMP) promote inhibitory processes, protecting the brain from the effects of stress. Opioid peptides (enkephalins) play a dual role: on the one hand, they can provoke seizures, and on the other hand, their release is associated with the specific feeling of euphoria experienced by some patients during the aura preceding a seizure.

During therapy, it is important to consider metabolic aspects. Many drugs induce folic acid deficiency, but its exogenous administration, as a rule, does not lead to an increased frequency of paroxysms. To block provoking alkalosis, a ketogenic diet (a diet rich in fats) and specific drugs that cause controlled acidosis (e.g., acetazolamide) are actively used, which significantly enhances the overall antiepileptic effect.

Metabolic shifts and negative symptoms

The clinical picture of epilepsy is not limited to convulsions. A crucial aspect is negative symptoms, which include specific personality changes. These manifestations are directly related to atrophic processes in the brain, which steadily increase against the background of chronic cerebral metabolic disorders.

During the seizure itself, the brain enters an extreme hypermetabolic state. The consumption of glucose and oxygen (O2) by tissues increases abruptly by 2–3 times. This process is accompanied by the massive and pathological accumulation of lactate, prostaglandins, and free fatty acids, which exerts a toxic effect on cells. In the interictal period, this picture changes radically, and the hypermetabolic state is replaced by a pronounced hypometabolic state, which in the long term leads to neuronal atrophy.

Diagnostics and differential search

Establishing an accurate diagnosis is based on identifying a typical clinical picture and the results of special instrumental studies. The most specific diagnostic criteria are considered to be the patient's characteristic personality changes and the presence of generalized seizures (absences, tonic-clonic seizures, and other forms).

Electroencephalography (EEG) remains the most important method for recording epileptiform activity. Signs indicating a lowered seizure threshold include high-amplitude sharp and slow waves, paroxysmal spikes, and classical "spike-wave" complexes. However, it is important to remember that such EEG phenomena can occur in 5–20% of absolutely healthy individuals, as well as in endogenous mental illnesses, such as schizophrenia. Therefore, the role of EEG boils down to confirming the clinical diagnosis (the clinical picture is always primary!), assessing the effectiveness of ongoing therapy, and searching for a local lesion.

Neuroimaging methods (MRI and CT) are not capable of revealing specific changes characteristic specifically of epilepsy. Nevertheless, their implementation is strictly necessary to rule to other organic pathologies.

Difficulties in diagnosis often arise with late-onset disease, mildly expressed personality changes, the absence of typical seizures, or the development of epileptic psychoses. Differential diagnosis is primarily carried out with organic diseases accompanied by epileptic syndrome: space-occupying processes (tumors, hematomas) and parasitic infestations (echinococcosis, cysticercosis).

Class and exam questions

What else to study on this topic

• Mechanisms of formation of atrophic processes and negative symptoms during the shift between hyper- and hypometabolic states.
• The role of opioid peptides (enkephalins) in the pathogenesis of epileptic aura and seizure provocation.
• Pharmacodynamics of valproates and barbiturates: impact on GABA metabolism.
• Differential diagnosis of epilepsy and parasitic brain lesions (cysticercosis, echinococcosis).
• The effect of purines and glycine on inhibitory mechanisms and brain protection from stress.

Other topics in "Chapter 20. Epilepsy"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.