Seizure is the transient occurrence of signs and/or symptoms due to abnormal, excessive, or synchronous neuronal activity in the brain. Signs or symptoms may include alterations of consciousness, motor, sensory, autonomic, or psychic events. Epilepsy is a condition characterized by the occurrence of two or more seizures that are not acutely provoked by other illnesses or conditions. Medications control rather than curing the seizure disorder. Adherence to the medication regimen is important.
Classification of Epileptic Seizures:
Epileptic seizures are classified as either focal or generalized, based on how the abnormal brain activity begins.
[I] Focal or Partial Seizures:
When seizures appear to result from abnormal activity in just one area of the brain, they are called focal (partial) seizures. These seizures fall into two categories.
1. Simple focal seizures:
These seizures do not result in loss of consciousness. They may alter emotions or change the way things look, smell, feel, taste or sound. They may also result in involuntary jerking of a body part, such as an arm or leg, and spontaneous sensory symptoms such as tingling, dizziness, and flashing lights.
2. Complex partial seizures:
Complex partial seizures are characterized by focal seizure activity accompanied by a transient impairment of the patient’s ability to maintain normal contact with the environment. The patient is unable to respond appropriately to visual or verbal commands during the seizure and has impaired recollection or awareness of the ictal phase. The seizures frequently begin with an aura (i.e., a simple partial seizure) that is stereotypic for the patient.
3. Dyscognitive focal seizures:
These seizures alter consciousness or awareness and may cause to lose awareness for a longer period. Dyscognitive focal seizures often result in staring and purposeless movements such as hand rubbing, chewing, swallowing, or walking in circles.
[II] Generalized Seizures (Convulsive or Non-convulsive):
Seizures that appear to involve all areas of the brain are called generalized seizures. Six types of generalized seizures exist.
1. Absence seizures (Petit Mal):
Petit Mal or Absence seizures are characterized by staring and subtle body movement. These seizures can cause a brief loss of awareness.
2. Tonic seizures:
Tonic seizures cause stiffening muscles. These seizures usually affect muscles in the back, arms, and legs and may cause them to fall to the ground.
3. Clonic seizures:
Clonic seizures are associated with rhythmic, jerking muscle movements. These seizures usually affect the neck, face, and arms.
4. Myoclonic seizures:
These usually appear as sudden brief jerks or twitches of arms and legs.
5. Atonic seizures:
Atonic seizures, also known as drop seizures, because a loss of muscle control, which may result in sudden collapse or fall.
6. Tonic-clonic seizures (Grand Mal):
Tonic-clonic seizures are characterized by a loss of consciousness, body stiffening and shaking, and sometimes loss of bladder control or biting tongue.
Status epilepticus is defined as either continuous seizures lasting at least 5 minutes, or two or more discrete seizures between which there is incomplete recovery of consciousness.
Febrile seizures occur in up to 8% of children between 6 months and 6 years of age. Long-term treatment or prophylaxis for simple febrile seizures is not recommended.
Unclassified epileptic seizures:
Not all seizure types can be classified as partial or generalized. This appears to be especially true of seizures that occur in neonates and infants. The distinctive phenotypes of seizures at these early ages likely result, in part, from differences in neuronal function and connectivity in the immature versus mature CNS.
There are over 2.5 million people diagnosed with epilepsy every year. Epilepsy is one of the most common serious neurological disorders affecting about 65 million people globally. It affects 1% of the population by age 20 and 3% of the population by age 75. It is more common in males than females with the overall difference being small. Most of those with the disease (80%) are in the developing world.
Epilepsy is usually present in childhood or adolescence but may occur for the first time at any age. About 5% of the population suffers a single seizure at some time. About 0.5-1% of the population have recurrent seizure epilepsy. About 70% of patients are well controlled with drugs (prolonged remissions) and 30% of epilepsy patients are at least partially resistant to drug treatments.
It is a symptom of numerous disorders, but in the majority of sufferers, the cause remains unclear despite careful history taking, examination and investigation.
Epilepsy has no identifiable cause in about half of those, with the condition. In about half the people with epilepsy, the condition may be traced to various factors.
Table: Causes of seizures
|Neonates (<1 month)||Perinatal hypoxia, ischemia, Intracranial hemorrhage and trauma, Acute CNS infection, Metabolic disturbances (hypoglycemia, hypocalcemia, hypomagnesemia, pyridoxine deficiency), Drug withdrawal, Developmental disorders, and Genetic disorders.|
|Infants and children (>1 month and <12years)||Febrile seizures, Genetic disorders (metabolic, degenerative, primary epilepsy syndromes), CNS infection, Developmental Disorders, Trauma, and Idiopathic.|
|Adolescents (12–18 years)||Trauma, Genetic disorders, Infection, Brain tumor, Illicit drug use and Idiopathic.|
|Young adults (18–35 years)||Trauma, Alcohol withdrawal, Illicit drug use, Brain tumor, and Idiopathic.|
|Older adults (>35 years)||Cerebrovascular disease, Brain tumor, Alcohol withdrawal, Metabolic disorders (uremia, hepatic failure, electrolyte abnormalities, hypoglycemia), Alzheimer’s disease, and other degenerative CNS diseases and Idiopathic.|
Some types of epilepsy, which are categorized by the type of seizure experienced, run in families. In these cases, there is likely a genetic influence.
Researchers have linked some types of epilepsy to specific genes, though it is estimated that up to 500 genes could be tied to the condition. For most people, genes are only part of the cause of epilepsy. Certain genes may make a person more sensitive to environmental conditions that trigger seizures.
Head trauma: Head trauma that occurs due to a car accident or other traumatic injury can cause epilepsy.
Brain conditions: Brain conditions that result in damage to the brain, such as brain tumors or strokes, also can cause epilepsy. Stroke is a leading cause of epilepsy in adults older than age 35.
Infectious diseases: Infectious diseases, such as meningitis, AIDS, and viral encephalitis, can cause epilepsy.
Prenatal injury: Before birth, babies are sensitive to brain damage that could be caused by several factors, such as an infection in the mother, poor nutrition, or oxygen deficiencies. This brain damage can result in epilepsy or cerebral palsy.
Developmental disorders: Epilepsy can sometimes be associated with developmental disorders, such as autism and neurofibromatosis.
Stroke and other vascular diseases: Stroke and other blood vessel (vascular) diseases can lead to brain damage that may trigger epilepsy.
Dementia: Dementia can increase the risk of epilepsy in older adults.
Mechanisms of Seizure Initiation and Propagation:
The hypersynchronous discharges that occur during a seizure may begin in a very discrete region of the cortex and then spread to neighboring regions. Seizure initiation is characterized by two concurrent events:
- high-frequency bursts of action potentials and 2) hyper synchronization of a neuronal population. The synchronized bursts from a sufficient number of neurons result in a so-called spike discharge on the EEG. At the level of single neurons, the epileptiform activity consists of sustained neuronal depolarization resulting in a burst of action potentials, a plateau-like depolarization associated with completion of the action potential burst, and then rapid repolarization followed by hyperpolarization. This sequence is called the paroxysmal depolarizing shift. The bursting activity resulting from the relatively prolonged depolarization of the neuronal membrane is due to the influx of extracellular Ca++, which leads to the opening of voltage-dependent Na+ channels, the influx of Na+, and the generation of repetitive action potentials. The subsequent hyperpolarizing after potential is mediated by GABA receptors and Cl− influx, or by K+ efflux, depending on the cell type.
Seizure propagation, the process by which a partial seizure spreads within the brain, occurs when there is sufficient activation to recruit surrounding neurons. This leads to a loss of surrounding inhibition and spread of seizure activity into contiguous areas via local cortical connections, and to more distant areas via long association pathways such as the corpus callosum.
The propagation of bursting activity is normally prevented by intact hyperpolarization and a region of surrounding inhibition is created by inhibitory neurons. With sufficient activation, there is a recruitment of surrounding neurons via several mechanisms. Repetitive discharges lead to:
1) an increase in extracellular K+, which blunts the extent of hyperpolarizing outward K+ currents, tending to depolarize neighboring neurons;
2) accumulation of Ca++ in presynaptic terminals, leading to enhanced neurotransmitter release; and
3) depolarization-induced activation of the NMDA subtype of the excitatory amino acid receptor, which causes more Ca++ influx and neuronal activation. Of equal interest, but less well understood, is the process by which seizures typically end, usually after seconds or minutes, and what underlies the failure of this spontaneous seizure termination in the life-threatening condition known as status epilepticus.
Because epilepsy is caused by abnormal activity in brain cells, seizures can affect any process that the brain coordinates. Both partial and generalized seizures at the same time, or one can precede the other. The symptoms can last anywhere from a few seconds to 15 minutes per episode.
Sometimes, symptoms occur before the seizure takes place. These include:
- A sudden feeling of fear or anxiousness,
- A feeling of being sick to your stomach,
- A change in vision,
- A jerky movement of the arms and legs that may cause you to drop things,
- An out of body sensation,
- A headache.
Symptoms that indicate a seizure is in progress include:
- Losing consciousness, which is followed by confusion,
- Having uncontrollable muscle spasms,
- Drooling or frothing at the mouth,
- Having a strange taste in the mouth,
- Clenching teeth,
- Biting of the tongue,
- Having sudden, rapid eye movements,
- Making unusual noises, such as grunting,
- Losing control of bladder or bowel function,
- Having sudden mood changes.
Tests and Diagnosis:
Physical examination helps in the diagnosis of specific epileptic syndromes that cause abnormal findings, such as dermatologic abnormalities. In addition, patients who for years have had intractable generalized tonic-clonic seizures are likely to have suffered injuries requiring stitches. Several tests to diagnose epilepsy and determine the cause of seizures includes.
A neurological examination looks at how well the brain and the rest of the nervous system are functioning and may test behavior, motor abilities, mental function, and other areas to diagnose the condition and determine the type of epilepsy.
Several blood tests may be recommended to check for signs of infections, genetic conditions, or other conditions like electrolyte imbalances which may be associated with seizures.
An electroencephalography test can help to diagnose a seizure. These tests measure brain waves. Viewing brain waves during a seizure can help to diagnose the type of seizure.
Imaging scans such as a Computerized tomography (CT) scan, Magnetic resonance imaging (MRI), Functional MRI (fMRI), Positron emission tomography (PET), or Single-photon emission computerized tomography (SPECT) also can help by providing a clear picture of the brain. These scans allow seeing abnormalities like blocked blood flow or a tumor.
These tests are performed to assess thinking, memory, and speech skills. The test results help to determine which areas of the brain are affected.
Treatments and Drugs:
The majority of epileptic seizures are controlled through drug therapy, particularly anticonvulsant drugs. The type of treatment prescribed will depend on several factors including the frequency and severity of the seizures as well as the person’s age, overall health, and medical history. An accurate diagnosis of the type of epilepsy is also critical to choosing the best treatment.
The different antiepileptic drugs (AEDs) act by affecting one or more of these processes. Specific mechanisms of action of the AEDs include:
- Modulation of voltage-dependent ion channels: Carbamazepine, Phenytoin, Valproic acid.
- Enhancement of activity of the major inhibitory neurotransmitter in the brain, GABA: Phenobarbital, Benzodiazepines, Tiagabine.
- Suppression of excitatory neurotransmission: Lamotrigine, Felbamate.
Surgery includes removal of the area of the brain causing the seizures.
Vagus nerve stimulation: The vagus nerve is stimulated to reduce the frequency and intensity of seizures. This can be suitable for some people with seizures that are difficult to control with medication.
Ketogenic diet: A diet very high in fat, low in protein, and almost carbohydrate-free. This can be effective in the treatment of difficult to control seizures in some children.
Table: Selection of antiepileptic drugs
|Primary Generalized Tonic-Clonic||Partial*||Absence||Atypical Absence, Myoclonic, Atonic|
|Valproic acid Lamotrigine Topiramate||Carbamazepine Phenytoin Lamotrigine Valproic acid||Valproic acid Ethosuximide||Valproic acid Lamotrigine Topiramate|
|Zonisamideb Phenytoin Carbamazepine Oxcarbazepine Phenobarbital Primidone Felbamate||Levetiracetam** Topiramate Tiagabine** Zonisamide** Gabapentin** Phenobarbital Primidone||Lamotrigine Clonazepam||Clonazepam Felbamate|
* Includes simple partial, complex partial, and secondarily generalized seizures.
** As adjunctive therapy
Table: Types and symptoms of epileptic seizures
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