Epilepsy Latest Facts: Pathophysiology, Causes, Types, and Treatments

What is epilepsy?

Epilepsy is a chronic, neurological disorder that is defined by the International League against Epilepsy (ILAE) as a ‘disease characterized by an enduring predisposition to generate epileptic seizures and by the neurobiological, cognitive, psychological, and social consequences of this condition.

Epilepsy

Epilepsy

Initially, epilepsy was considered a disorder since it is a heterogeneous condition but in 2005, the executive committees of ILAE decided to change that and define it as a disease instead, to connote the seriousness of the condition to the public.

It is important to not mistaken epilepsy with seizures, which are defines by the ILAE as ‘a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.’

Epilepsy is characterized by unprovoked and recurrent seizures that affect approximately 65 million people worldwide. In the United States alone, there are 3 million affected people and the number is steadily increasing to approximately 150,000 new cases per year.

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Around one percent of the affected individuals worldwide may be affected by sudden unexplained death. The elderly affected by epilepsy have a higher risk of stroke and generally, 50 percent to 70 percent of people with epilepsy develop depression, anxiety, or both.

Epilepsy affects individuals of all ages and both genders. It has no predilection for any gender however, there is a difference in age of onset, depending on the country of origin of the affected person. In developed countries, new cases are diagnosed in babies and the elderly whereas, in developing countries, new cases are diagnosed in older children and young adults. This discrepancy based on countries is due to the difference in etiology and triggers in different countries.

What are the Types of Epileptic Seizures?

Seizures are generally classified into two broad categories, based on the brain area involved; Focal (partial) seizure, which includes only parts of the brain, and Generalized seizure, which affects the entire brain.

Focal Seizures

Simple partial seizure

This type of seizure presents with the following symptoms:

  • Dizziness
  • Altered sense of taste, smell, sight, hearing, or touch
  • Tingling and twitching of limbs

Important to note that there is no loss of consciousness in this type of seizure, unlike the other types.

Complex partial seizure

This type involves loss of consciousness and awareness and presents with the following symptoms:

  • Staring blankly
  • Unresponsiveness
  • Repetitive movements

Generalized Seizures

These types of seizures are divided into six types and affect the entire brain:

  • Absence Seizures: Also known as petit mal seizures, they are a blank stare type of seizures associated with loss of awareness.
  • Tonic Seizures: This type of seizure causes muscle stiffness and rigidity.
  • Clonic Seizures: This type of seizure causes repetitive jerking movements.
  • Atonic Seizures: Opposite of the tonic seizures, this type is associated with loss of muscle tones and abrupt falls.
  • Myoclonic Seizures: Not to be confused with clonic seizures, this type is associated with spontaneous quick twitching of arms or legs.
  • Tonic-clonic Seizures: Also known as grand mal seizures, this type is a combination of tonic and clonic seizures and presents with the following symptoms :

● stiffening of the body
● shaking
● loss of bladder or bowel control
● biting of the tongue
● loss of consciousness

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What are the Risk Factors for Epilepsy?

There are several risk factors for the development of epilepsy, all of which are not necessarily present in most patients. However, knowing them can help with an earlier diagnosis of epilepsy.

● Babies who are born small for their age
● Babies who have seizures in the first month of life
● Babies who are born with abnormal areas in the brain
● Bleeding into the brain
● Abnormal blood vessels in the brain
● Serious brain injury or lack of oxygen to the brain
● Brain tumors
● Infections of the brain: abscess, meningitis, or encephalitis
● Stroke resulting from blockage of arteries
● Cerebral palsy
● Conditions with intellectual and developmental disabilities
● Seizures occurring within days after head injury (“early posttraumatic seizures”)
● Family history of epilepsy or fever-related seizures
● Alzheimer’s disease
● Autism spectrum disorder
● Fever-related (febrile) seizures that are unusually long
● Status epilepticus (prolonged and refractory episode of seizures) can be present without the diagnosis of epilepsy however, it can increase the risk of epilepsy development.
● Use of recreational and illegal drugs such as cocaine

What are the Causes of Epilepsy?

Epilepsy has several etiologies, all of which can be divided into two categories; genetic epilepsy and acquired epilepsy. However, it is important to note that 6 out of 10 epileptic patients may never be able to determine a cause for their epilepsy.

Genetic Epilepsy

Epilepsy runs in family and there are over 500 genes related to a diagnosis of epilepsy. If an identical twin is diagnosed with epilepsy, there is a 50 percent to 60 percent chance that the other twin will also be affected by epilepsy.

The genes that are usually affected in epilepsy are responsible for the encoding of G protein-coupled receptors (GPCRs), ion channels, GABA, and other enzymes. The effect of genetics on epilepsy development may be direct or indirect.

Directly, approximately 1 percent to 2 percent of epilepsy cases worldwide are due to single gene defects, although most are due to the interaction between multiple defective genes and several environmental factors.

Indirectly, genetics provides every individual with a threshold called, seizure threshold. The level of an individual’s threshold point decides how sensitive the person is to epileptic triggers. A person with a higher threshold has less risk of having seizures, whereas a person with a lower threshold is more likely to get seizures.

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Acquired Epilepsy

This type of epilepsy is not something a person is born with but instead is a result of other conditions that may affect the brain. These conditions include but are not limited to:

  • Traumatic brain injury or head trauma
  • Scarring on the brain after a brain injury (post-traumatic epilepsy)
  • A high fever (can cause febrile seizures)
  • Stroke (the leading cause of epilepsy in people over the age of 35 years)
  • Vascular diseases like Cerebral Arteriovenous Malformations
  • Hypoxia (lack of oxygen to the brain)
  • Brain tumor or cyst
  • Neurodegenerative disorders like Alzheimer’s disease
  • Infectious diseases such as AIDS and meningitis
  • Genetic or developmental disorders like Down Syndrome
  • Neurological disorders like Neurofibromatosis

Furthermore, traumatic incidents like lack of oxygen during birth can also result in the development of seizures in babies. Another important acquired cause of epilepsy in babies is a prenatal injury in the form of maternal infection or malnutrition or prenatal hypoxia. However, these causes can also cause cerebral palsy, which is a risk factor for epilepsy. Also, maternal use of certain teratogens during pregnancy can also result in seizure development in babies.

What are the epilepsy triggers?

Epileptic seizures are often triggered by certain situations or conditions that can be identified by the patient using an epilepsy journal. The patient must write down the following information in their epilepsy journal after each epileptic seizure:

  • The seizure began at what time and on what day
  • What was the patient doing at that moment?
  • What was happening in the patient’s surroundings
  • Any unusual sights, smells, or sounds
  • Any unusual stressors
  • Was the patient eating, if yes then what were they eating. If no, then how long had it been since their last meal
  • Quality of sleep the night before
  • Level of fatigue and tiredness at the time of seizure

To figure out one’s own triggers, journaling is very important to keep track of. Some common triggers include:

  • Lack of sleep
  • Illness or high fever
  • High-stress situations
  • Bright lights, flashing lights, or patterns
  • Caffeine, alcohol, certain medicines, or drugs
  • Skipping meals, overeating, or specific food ingredients

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What is the pathophysiology of epilepsy?

Epilepsy is a neurological disease that affects the ability of neurons to fire up and transmit electrical signals for the proper functioning of the human body. The neurons are the building blocks of the brain and they transmit electrical signals non-synchronously, so that information can be transmitted in proper order.

This transmission of information in the form of electrical signals is regulated by factors within the neuron and factors within the environment surrounding the neurons. Neuronal factors include the type and number of ion channels, changes to receptor proteins, and the change in gene expression. Neurotransmitter regulation and spasticity are the factors in the surroundings of neurons that can affect information transmission.

In epilepsy, the asynchronous information transmission becomes synchronized with all neurons firing information at the same time, the reason for which is not exactly known. However, it is known that in epilepsy, the excitatory neurons fire without any resistance, which may be due to changes in ion channels or lack of proper function of inhibitory neurons. These are theorized to be the main causes of epilepsy.

The defective ion channels and synchronous neuronal firing result in the development of a seizure focus area which is basically the area from where seizures originate.

How can epilepsy be diagnosed?

The diagnosis of epilepsy depends on clinical observation of the seizure onset and typing along with a complete neurological examination. Accurate classification of seizures based on their typing is the first step in the diagnosis and quite a crucial step at that too.

After clinical observation and history taking, both personal and family, further workup can be done using certain tests like EEG, blood tests, and neuroimaging techniques.

The newest definition of epilepsy states that the presence of any of the following conditions can be used to diagnose epilepsy definitely:

  • At least two unprovoked (or reflex) seizures occurring more than 24 hours apart
  • One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years
  • Diagnosis of an epilepsy syndrome

Following this, the physician might ask for blood tests to check for kidney and liver function tests along with blood glucose levels to eliminate other causes for seizures.

The most common test done to diagnose epilepsy is EEG or electroencephalogram. For this test, electrodes are attached to the scalp of the patient to monitor the electrical activity of the brain. If the patient has epilepsy, the electrical activity will be severely altered, showing abnormal functioning of the brain.

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To determine the exact areas of the brain affected by seizures, a variant of EEG called high-density EEG can be performed. In this type, the electrodes are placed closer than in a normal EEG.

A CT scan, MRI, functional MRI, and PET scan can also be performed for better visualization of the brain and the areas affected by epilepsy.

What are the differential diagnoses of epilepsy?

Diagnosing a person with epilepsy is difficult since patients don’t always present with straightforward cases. Furthermore, several conditions of different etiologies and origins can result in similar symptoms hence requiring detailed tests to eliminate other causes of symptoms.

The differential diagnoses of epilepsy include:

● Syncope
● Hyperventilation
● Migraines
● Narcolepsy
● panic attacks and
● psychogenic non-epileptic seizures (PNES)

Certain types of epilepsy are commonly mistaken as other disorders, for example, nocturnal frontal lobe epilepsy is commonly misdiagnosed as nightmares. An accurate diagnosis is crucial for accurate treatment and management of epilepsy.

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Classification of Epilepsy by ILAE 2011

  • Unknown cause (mostly genetic or presumed genetic origin)
    • Pure epilepsies due to single-gene disorders
    • Pure epilepsies with complex inheritance
  • Symptomatic (associated with gross anatomic or pathologic abnormalities)
    • Mostly genetic or developmental causation
      • Childhood epilepsy syndromes
      • Progressive myoclonic epilepsies
      • Neurocutaneous syndromes
      • Other neurologic single-gene disorders
      • Disorders of chromosome function
      • Developmental anomalies of cerebral structure
    • Mostly acquired causes
      • Hippocampal sclerosis
      • Perinatal and infantile causes
      • Cerebral trauma, tumor, or infection
      • Cerebrovascular disorders
      • Cerebral immunologic disorders
      • Degenerative and other neurologic conditions
  • Provoked (a specific systemic or environmental factor is the predominant cause of the seizures)
    • Provoking factors
    • Reflex epilepsies
  • Cryptogenic (presumed symptomatic nature in which the cause has not been identified)

Treatment of Epilepsy

Epilepsy can be managed and treated using one or more of the four ways mentioned below:

1. Medications

Anti-seizure medication is the first-line treatment for epilepsy and they are very efficient in reducing the frequency and severity of seizures. Furthermore, the medications can be taken in pill, liquid, or injectable forms that need to be taken twice a day, starting with the lowest dose and then increasing the dose slowly.

Some of the anti-seizure medications usually prescribed include:

  • Levetiracetam (Keppra)
  • Lamotrigine (Lamictal)
  • Topiramate (Topamax)
  • Valproic acid (Depakote)
  • Carbamazepine (Tegretol)
  • Ethosuximide (Zarontin)

Like any medications, they carry certain side effects like fatigue, memory problems, skin rash, and poor coordination.

2. Surgery

Epileptic surgery is an option for patients who have tried all other forms of treatment without any viable results. The surgery usually includes resection of the area where seizures start, which most of the time is the temporal lobe. In that case, the surgery is called a temporal lobectomy. Often, the surgeons prefer to keep the patient awake for this surgery to be able to communicate with the patient and confirm that only the affected area is being removed and not surrounding areas important for speaking, hearing, vision, and so on.

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If the seizure focus area is too large to be removed, then a procedure called multiple subpial transections or disconnection may be performed which involves cutting off of neural pathways to the area, stopping the spread of epilepsy.

However, surgery for epilepsy carries the risk of cognitive changes and hence, should be discussed in detail before the decision is made.

3. Vagus Nerve Stimulator

In this therapeutic option, a device called a vagus nerve stimulator is implanted in the chest of the patient. This implant has wires attached to the vagus nerve, sending electrical signals to it. Although the exact mechanism of the functioning of the implant isn’t understood, it was shown to reduce seizures by 20 percent to 40 percent.

4. Dietary Changes

Children with epilepsy are known to benefit from the ketogenic diet, a high fat, low carb, adequate-protein diet. However, it isn’t beneficial for all and it may not work for certain types of seizures.

Adolescents and young adults with epilepsy may benefit from a modified Atkins diet, high fat, and controlled carbohydrates diet. In fact, most adults on this diet have reduced seizures.

However, it is important to note that since these diets are low in carbohydrates and fibers, constipation is often a common side effect.

What is the prognosis of epilepsy?

Epilepsy is not a curable but a manageable disease with almost 80% of people responding to one of the therapeutic options mentioned above. However, people with epilepsy are also at a higher risk of death, almost 1.6 to 4.1 times more risk than an average person.

New Research

Scientists worldwide are trying to figure out a way to predict seizures or forecast them depending on the EEG findings. However, no promising results have been reported yet.

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References

https://www.epilepsy.com/learn/about-epilepsy-basics/facts-about-seizures-and-epilepsy

https://www.cdc.gov/epilepsy/about/fast-facts.htm

https://www.ninds.nih.gov/Disorders/All-Disorders/Epilepsy-Information-Page

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