Epilepsy and Seizures
Epilepsy is a common neurologic condition in which neurons and neuronal networks malfunction to cause the sometimes dramatic symptoms of seizures. Epilepsy usually results in unpredictable, unprovoked recurrent seizures that affect a variety of mental and physical functions. Epileptic seizures are manifested by an abnormal, excessive, and hypersynchronous electrical discharge of neurons in the brain.
Approximately 75% of epilepsy begins in childhood, reflecting the heightened susceptibility of the developing brain to seizures. Also, epilepsy is one of the nervous system diseases in the elderly, second to dementia and stroke. Geriatric epilepsy includes pre-elderly epilepsy continuing to the old age stage and new-onset epilepsy in the elderly. People without epilepsy can experience symptomatic seizures-the structure and function of the brain carries the risk of generating seizures if exposed to convulsant drugs or conditions.
A seizure is a transient epileptic event, indicating a disturbance in brain function and last from a few seconds to a few minutes. It includes a series of signs or symptoms, such as convulsions, brief loss of consciousness, blank staring, isolated posturing, or jerking of a single limb. Other possible conditions include sleep disorders, panic attacks, migraines, cataplexy, recurrent transient global amnesia, and psychogenic pseudoseizures.
Epilepsy and seizure have numerous causes, each reflecting underlying brain dysfunction. Head trauma and genetic cause are common causes of epilepsy. New-onset epilepsy in the elderly mainly results from accumulated brain injuries and other secondary factors. The most common acquired etiologies include cerebrovascular diseases, degenerative disorders associated with cognitive impairment, CNS tumors, and traumatic head injury. In addition, metabolic disturbances such as electrolyte imbalances, hypoglycemia or hyperglycemia, endocrine disorders, hematological disorders, renal failure, and hepatic failure may cause seizures at any age.
Fig.1 Classification of the epilepsies. (Falco-Walter, 2018)
There has been an explosion of information about the genetic basis of epilepsy syndromes. The most common form of generalized-onset epilepsy appears to be a polygenic disease. Expression of the phenotype requires the simultaneous inheritance of multiple genes. A speciﬁc disease-causing variant in a gene or copy number variant is believed to be pathogenic for epilepsy. Both monogenic and polygenic mutations lead to epilepsy. Genetic pathologies leading to epilepsy can occur anywhere from the circuit level (e.g., abnormal synaptic connectivity) to the receptor level (e.g., abnormal γ-aminobutyric acid [GABA] receptor subunits) to abnormal ionic channel function (e.g., potassium channel mutations). As knowledge of genetic factors expands, there is hope that syndrome-specific therapeutic interventions can be designed.
Autoimmune disease is one of the causes of new-onset epilepsy. Epilepsy and autoimmune encephalitis have been linked to neuronal intracellular antibodies (GAD65, ANNA-1, and Ma) and neuronal cell surface antibodies (VGKC complex, NMDAR, AMPA, GABA-B, and GluR5).
Diagnosis and Treatment
Many seizures, characteristic behavioral changes, and electrophysiological disturbances can usually be detected in scalp electroencephalographic (EEG) recordings. Others such as normal MRI and neurologic examination can also be used for recognizing the seizure. Since the genetic basis of epilepsies becomes progressively unraveled, clinical testing will occupy an increasingly pivotal role in the clinic.
Once epilepsy is established, AEDs are the first line of treatment. Each distinct form of epilepsy has its natural history and response to treatment. After a first seizure, the risks of future seizure recurrence must be weighed against the risks and benefits of starting antiepileptic drugs (AEDs). If medication fails to control seizures, there are other options for epilepsy control, including resective epilepsy surgery (lesionectomy, hemispherotomy) and palliative epilepsy surgery (stimulation therapy, callosotomy).
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- Falco-Walter, J. J.; et al. The new definition and classification of seizures and epilepsy. Epilepsy research. 2018, 139, 73-79.