Epileptic Seizures: Mechanisms and Characteristics

Introduction

In neurology, the study of epileptic seizures is important. Focal and generalized seizures with their unique subtypes are two primary forms of seizures. Focal (otherwise known as partial) seizures are confined to one area of the cerebral cortex, with one area of the body affected at the start. Generalized seizures are greater and diffuse in different regions of the brain. This paper will explore the underlying mechanisms and characteristics of each type of seizure.

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Pathophysiology

Seizures are commonly caused by disorderly, excessive, and episodic neuronal activity. Seizures can start as focal and spread to become generalized. However, the pathophysiology between the two differs as cellular excitability and synchronization mechanisms are varied in focal seizures (Kumar & Sharma, 2019). Focal seizures are characterized by a spike in the focal interictal epileptiform. The cellular neurophysiological correlate results in interictal focal epileptiform discharge in a paroxysmal depolarization shift (PDS) (Ko, 2019).

This is demonstrated by an extended calcium-dependent depolarization which leads to a hyperpolarized membrane potential. Commonly calcium-dependent potassium channels mediate after-hyperpolarization, but when multiple neurons begin PDS synchronously, an interictal spike occurs. Generalized seizures are best characterized by the pathophysiologic mechanism of thalamocortical interaction. The thalamocortical circuit has steady rhythms with periodic spikes of increased inhibition. When the rhythms are altered this leads to generalized-onset seizures as thalamic relay neurons receive inputs from the spinal cord and deviate them to neocortical pyramidal neurons (Ko, 2019).

Thalamic relay neurons receive activation by GABA proteins leading to hyperpolarization which modifies T-calcium channels into a closed state and asynchronous opening of many T-calcium channels every 100 milliseconds which creates oscillations (Ko, 2019).

Examples

Focal seizures can be categorized as simple focal or complex focal. In simple focal seizures, awareness is retained, with motor and sensory reactions such as jerking, spasms, and muscle rigidity with senses being mildly affected as well. Complex focal seizures are primarily differentiated by the individual losing consciousness or awareness, with some of the above symptoms potentially present along with automatisms. There are six types of generalized seizures in total including generalized tonic-clonic, absent, myoclonic, clonic, tonic, and atonic. The most common is a generalized tonic-clonic which leads the individual to lose consciousness and collapse.

The body stiffens, which is the tonic stage, and then begins to jerk (the clonic phase) after which the person does into a deep sleep of the postictal phase. On the other hand, an absence seizure is milder, leading to loss of consciousness for a few seconds, with little to no other symptoms. However, this type of generalized seizure is more sporadic and may occur up to several times a day (Carcak & Ozkara, 2018).

EEG Findings

Focal EEG changes can be characterized as either epileptiform or non-epileptiform. Commonly focal seizures are epileptiform, with characteristics such as spikes and sharp waves which indicate the focus of the seizures. Non-epileptiform types can be viewed in alterations in normal rhythms. Partial seizures demonstrate interictal epileptiform abnormalities, periodic lateralized discharges, and ictal patterns. No matter the type, a partial seizure begins with an evident delineation of onset activity different from the preceding background, which evolves in frequency and amplitude, and eventually dies down to normal background activity (Attarian & Undevia, 2011).

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Generalized seizures are also characterized by interictal epileptiform discharges (IEDs) which present as typical or abnormal generalized spike-wave complexes or polyspike-wave discharges. Focal spike-wave discharges can sometimes be seen in generalized seizures as well (Britton, Frey, & Hopp, 2016).

Physical Presentation

Depending on the type of focal seizure, an individual may or may not lose consciousness and awareness, with different impacts on memory afterward. Since focal seizures affect a specific part of the brain there are different physical presentations. Muscle contractions occur in one part or side of the body. A patient may experience numbness or tingling. A rapid heart rate, nausea, and sweating are common. Some people experience pain or unusual movements.

If a specific part of the brain is affected, there may be changes in vision ranging from blackouts to hallucinations. Generalized seizures lead to more comprehensive physical characteristics, with loss of consciousness most often. Depending on the type, there may be stiffening and jerking of limbs and muscle contractions, rapid contractions on both or one side of the body, or a complete loss of muscle tone. Breathing patterns may change during various phases of the seizure (Carcak & Ozkara, 2018).

Medications

Medications for seizures are chosen based on the type of seizure, patient profile, and side effects. For focal seizures, it is necessary to use first-line antiepileptic drugs (AED), the most common of which are carbamazepine and lamotrigine. Additionally, valproate, oxcarbazepine, and levetiracetam may be used if there are problems with other medications not being tolerated (Kumar & Sharma, 2019). The general medications for generalized tonic-clonic seizures include valproic acid, lamotrigine, and topiramate.

Levetiracetam may also be used in patients aged 6 and older. The AED medication treatment is the primary course of action for most patients, with four primary objectives of eliminating seizures or lowering their frequency, avoiding adverse effects, aiding patients to restore psychosocial activity, and helping to maintain a healthy normal lifestyle. AED’s are commonly introduced early on in treatment to avoid recurrences. Furthermore, antiepileptic therapy and lifestyle modifications are often helpful as either a concurrent treatment or for those patients where AEDs are ineffective or cause significant side effects (Goldenberg, 2010).

Conclusion

Although focal and generalized seizures share some similarities, it is evident they are inherently different. They have different origins and pathophysiological mechanisms, resulting in varying effects on patients. The physical symptoms and EEG results also differ slightly, allowing physicians to address the seizures accordingly. Treatment is similar to AED medication, but the drugs vary between the types.

References

Attarian, H. P., & Undevia, N. S. (2012). Atlas of electroencephalography in sleep medicine. New York, NY: Springer-Verlag.

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Britton, J.W., Frey, L.C., & Hopp, J.L. (2016). Electroencephalography (EEG): An introductory text and atlas of normal and abnormal findings in adults, children, and infants. E.K. St. Louis & L.C. Frey (Eds). Chicago, IL: American Epilepsy Society.

Carcak, N., & Ozkara, C. (2018). Seizures and antiepileptic drugs: From pathophysiology to clinical practice. Current Pharmaceutical Design, 23(42), 6376–6388. Web.

Goldenberg, M. M. (2010). Overview of drugs used for epilepsy and seizures. Pharmacy and Therapeutics, 35(7), 392-415. Web.

Ko, D. (2019). Epilepsy and seizures. Web.

Kumar, A., & Sharma, S. (2019). Simple partial seizure. Web.

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