Saturday, April 13, 2024

EMS Neurological Emergencies - Seizure Disorder Pathophysiology


The pathophysiology of seizures involves complex changes in the electrical activity of the brain, leading to abnormal synchronization of neuronal firing and the generation of seizure activity. 

While the precise mechanisms underlying seizures can vary depending on the type of seizure and the underlying cause, there are several key components involved in the pathophysiology of seizures:

Neuronal Hyperexcitability: Seizures are characterized by abnormal, excessive, and synchronous neuronal activity in the brain. 

This hyperexcitability can arise from various factors, including changes in ion channel function, neurotransmitter imbalance, or alterations in neuronal connectivity.

Ion Channel Dysfunction: Ion channels play a crucial role in regulating the flow of ions (such as sodium, potassium, calcium, and chloride) across neuronal cell membranes, which is essential for maintaining normal neuronal excitability and function. 

Dysfunction of ion channels, either through genetic mutations or acquired alterations, can lead to abnormalities in neuronal excitability and contribute to seizure generation.

Imbalance of Excitatory & Inhibitory Neurotransmission: Normal brain function relies on a delicate balance between excitatory and inhibitory neurotransmission. 

Excitatory neurotransmitters, such as glutamate, promote neuronal activation, while inhibitory neurotransmitters, such as gamma-aminobutyric acid (GABA), dampen neuronal activity. 

Imbalances in the relative levels or function of these neurotransmitters can disrupt the normal inhibitory control of neuronal firing and contribute to seizure generation.

Aberrant Synchronization of Neuronal Firing: Seizures result from the abnormal synchronization of neuronal firing, leading to hypersynchronous activity within neuronal networks. This synchronized firing can spread rapidly throughout the brain, resulting in the characteristic clinical manifestations of seizures.

Network Dysfunction: Seizure activity often involves multiple brain regions and networks. 

Abnormalities in the connectivity and communication between different brain regions can facilitate the propagation of seizure activity and contribute to the generation of seizures.

Excitotoxicity & Neuroinflammation: Prolonged or recurrent seizure activity can lead to excitotoxicity, a process in which excessive release of excitatory neurotransmitters, such as glutamate, results in neuronal damage and cell death. 

Additionally, seizures can trigger neuroinflammatory processes, further exacerbating neuronal dysfunction and contributing to seizure generation.

Structural & Metabolic Factors: Structural abnormalities in the brain, such as tumors, vascular malformations, or cortical dysplasia, can disrupt normal neuronal circuitry and increase the likelihood of seizure activity. 

Metabolic disturbances, such as hypoglycemia, electrolyte imbalances, or mitochondrial disorders, can also trigger seizures by affecting neuronal function.

Overall, the pathophysiology of seizures involves a complex interplay of genetic, molecular, cellular, and network-level processes that lead to abnormal neuronal excitability and synchronization. 

Understanding these mechanisms is essential for developing targeted therapies aimed at preventing or controlling seizure activity.

Further Reading:

Bledsoe, B. E., Cherry, R. A. & Porter, R. S (2023) Paramedic Care: Principles and Practice (6th Ed) Boston, Massachusetts: Pearson

Huff, J.S. & Murr, N (2023) Seizure. Treasure Island, Florida: StatPearls Publishing https://www.ncbi.nlm.nih.gov/books/NBK430765/ Accessed April 24, 2024

Peate, I. & Sawyer, S (2024) Fundamentals of Applied Pathophysiology for Paramedics. Hoboken, New Jersey:  Wiley Blackwell

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