1. Epilepsy
Babylonian medical treatise that dates back to B.C., which calls it miqtu (disease that makes one fall) and accurately describes its main clinical expressions

2. The most common recognized causes of epilepsy are:
Epilepsy is a common chronic neurological disorder characterized by recurrent unprovoked غير مبررseizures.
Seizures are transient signs and/or symptoms of abnormal, excessive or synchronous neuronal activity in the brain.
Epilepsy is incidence is higher in developing countries, the 100 to 190 cases per 100,000 persons per year, possibly related to poor health care and prenatal care, increased risk of neurologic trauma, and increased rates of infections.
Etiology
For nearly 80% of patients with epilepsy the underlying etiology is unknown.
The most common recognized causes of epilepsy are:
1. Head trauma and stroke.
2. Developmental and genetic defects (5% of cases)
3. Central nervous system (CNS) tumors, infections, and neurodegenerative diseases.
4. Human immunodeficiency virus infection or neuro-cysticercosis infection.
Isolated seizures that are not epilepsy can be caused by:
 stroke, metabolic disturbances (e.g., hyponatremia, hypoxia and hypoglycemia), and kidney failure, hypertensive encephalopathy, meningitis. If these underlying causes of seizures are not corrected, they may lead to the development of recurrent seizures or epilepsy.

3. Some drugs that are commonly associated with seizures include tramadol(treat moderate to severe pain), bupropion (antidepressant) theophylline (bronchodilator), PATHOPHYSIOLOGY Seizures Regardless of the underlying etiology, all seizures involve a sudden electrical disturbance of the cerebral cortex. A population of neurons fires rapidly and repetitively for seconds to minutes. Cortical electrical discharges become excessively rapid, rhythmic, and synchronous. This phenomenon is presumably related to an excess of excitatory neurotransmitter action, a failure of inhibitory neurotransmitter action, or a combination of the two. In the individual patient, however, it is usually impossible to identify which neuro -chemical factors are responsible.

4. Neurotransmitters
Glutamate:
The major excitatory neurotransmitter in the cerebral cortex is glutamate.
When glutamate is released from a pre-synaptic neuron, it attaches to one of several receptor types on the postsynaptic neuron. The result is opening of membrane channels to allow sodium or calcium to flow into the postsynaptic neuron, thus depolarizing it and transmitting the excitatory signal.
Many antiepileptic drugs (e.g., phenytoin, carbamazepine, and lamotrigine) work by interfering with this mechanism, either by:
 Glutamate antagonist (Blocking the release of glutamate)
 Reduce inward positive current (Blocking the sodium or calcium channels, thus preventing excessive excitation)
These drugs typically do not block normal neuronal signaling, only the excessively rapid firing characteristic of a seizure. For this reason they do not usually affect normal brain function.
The hippocampus which contains a large volume of just such glutamanergic neurons are especially vulnerable to epileptic seizure, subsequent spread of excitation, and possible neuronal death.

5. γ-amino-butyric acid (GABA): The major inhibitory neurotransmitter in the cerebral cortex is γ-amino- butyric acid (GABA) It attaches to neuronal membranes and opens chloride or potassium channels. When chloride flows into or potassium out the neuron , the neuron becomes hyperpolarized and less excitable. This mechanism is probably critical for shutting off seizure activity by controlling the excessive neuronal firing. Some antiepileptic drugs, primarily (e.g. barbiturates and benzodiazepines), work by enhancing the action of GABA. Cortical function is modulated by many other neurotransmitters. However, their role in the patho-physiology of epilepsy and in the action of antiepileptic drugs is not yet well known.

6. Neuronal Mechanisms 1. Seizures originate in a group of neurons that do not normal electrical behavior. Presumably, this is due to an underlying imbalance of neurotransmitter function as described above. 2. At the level of the individual neuron, Instead of firing a single action potential firing is  excessively  prolonged (firing a train of many action potentials) and  repetitive  stay depolarized too long,. This long, abnormal depolarization is called a paroxysmal depolarizing shift (PDS). The neurons involved may not be abnormal themselves, but are diverted from their normal functioning to participate in the wildly excessive discharges. 3. The excessive electrical discharges can spread to other neurons, either adjacent ones or distant ones connected by fiber tracts. The seizure thus spreads to other areas of the brain, recruiting them into the uncontrolled firing pattern. The degree of spread and the location of brain areas involved determine the clinical manifestations of the seizure. 4. Nearly all seizures stop spontaneously, because after seconds to minute's brain inhibitory mechanisms become strong enough to shut off the abnormal excitation.

7. Pathophysiology of epilepsy:  Epileptogenesis: Epileptogenesis is the gradual process by which a normal brain develops epilepsy. Epileptogenesis means permanent change in cortical function which renders أدى neurons more likely to participate شارك in a seizure discharge. Epileptogenesis exact way in which it occurs is not known. Epileptogenesis in animals (may be in humans) occurs after prolonged, repeated, low-level intermittent electrical stimulation of animal brains and is known as kindling تهيج. ▼ permanent increases in seizure susceptibility: in other words, a permanent decrease in seizure "threshold." Chemical stimulation Chemical stimulation can also induce seizures; repeated exposures to some pesticides have been shown to induce seizures in both humans and animals. One mechanism proposed for this is called excitotoxicity. The roles of kindling and excitotoxicity, if any, in human epilepsy are currently hotly debated. Other causes of epilepsy are brain lesions, where there is scar tissue or another abnormal mass of tissue in an area of the brain.

8. The seizures themselves may cause
 Some damage to the cortex;
 Loss of neurons, especially inhibitory neurons, has been demonstrated in tissue from seizure foci.
 Reorganization of connections between groups of neurons may strengthen excitatory connections and weaken inhibitory connections, making the occurrence of future seizures more likely.
Additionally, epilepsy is associated with an increased mortality rate. For these reasons, an argument can be made for controlling epileptic seizures with medications as early as possible. This may reduce the possibility of permanent changes in brain function, although this hypothesis is unproven.
The International Classification of Epileptic Seizures:
The International Classification of Epileptic Seizures combines the clinical description with certain electro-physiologic findings to classify epileptic seizures.
Seizures are divided into two main patho-physiologic groups: partial seizures and generalized seizures by EEG recordings and clinical symptomatology

9. A. Partial Seizures
When the seizure begins in a localized area of the brain, it is defined as partial.
Most often, focal epilepsy results from some localized organic lesion or func­tional abnormality, such as
(1) scar tissue in the brain that pulls on the adjacent neuronal tissue,
(2) a tumor that com­presses an area of the brain,
(3) a destroyed area of brain tissue, or
(4) congenitally deranged local circuitry.
These lesions can promote extremely rapid discharges in the local neurons; ▼
when the discharge rate rises above several hundred per second, synchronous waves begin to spread over adjacent cortical regions.
These waves presum­ably result from localized reverberating circuits that may gradually recruit adjacent areas of the cortex into the epi­leptic discharge zone.
The process spreads to adjacent areas at a rate as slow as a few millimeters a minute to as fast as several centimeters per second.
Focal seizures can spread locally from a focus or more remotely ابعدto the contralateral cortex and subcortical areas of the brain through projections to the thalamus, which has widespread connections to both hemispheres.

10. Partial Epileptic Seizures classified into:
1. Simple (formally called focal):
Focal seizures originate in one area of the brain, usually the cortex or limbic system.
The person having a focal seizure will not lose consciousness during the seizure, but will be unable to control various body movements.
People experiencing a simple partial seizure can talk and answer questions.
They will remember what happened during the seizure
Simple partial seizures usually last two to 10 seconds, although they may last longer.
If there are no convulsions, they may not be obvious to the onlooker.
Simple partial sei­zures may be preceded by an aura, with sensations such as fear, followed by motor signs, such as rhythmic jerking or tonic stiffening movements of a body part.
The type of simple partial seizure

11. A. Partial (focal) motor seizure
Simple partial seizures include convulsive (clonic, jerking) movements.
Jerking typically begins in one area of the body — the face, arm, leg, or trunk — and may spread to other parts of the body.
These seizures are sometimes called Jacksonian motor seizures; their spread is called a Jacksonian march. It cannot be stopped.
B. Partial (focal) somatosensory seizure
Some simple partial seizures consist of a sensory experience. The person may
see lights,
hear a buzzing sound, or
feel tingling or numbness in a part of the body.
These seizures are sometimes called Jacksonian sensory seizures.

12. C. Partial psychomotor seizure
Simple partial seizures which arise in or near the temporal lobes often take the form of an odd experience.
One may see or hear things that are not there
objects looking strange or appearing bigger or smaller than usual,
a feeling of having experienced events before, known as déjà vu French meaning "already seen"(as if something you have see or hear before).
One feels emotions, often fear, but sometimes sadness, anger, or joy.
There may be a bad smell or a bad taste,
a funny feeling in the pit of the stomach or a choking sensation.

13. D. Autonomic Seizures
These seizures are accompanied by autonomic symptoms or signs, such as
abdominal discomfort or nausea which may rise into the throat (epigastric rising),
stomach pain,
the rumbling sounds of gas moving in the intestines (borborygmi),
belching, and vomiting.
flatulence,
This has sometimes been referred to as abdominal epilepsy.
Other symptoms may include
pallor,
flushing,
sweating,
hair standing on end (piloerection), and
dilation of the pupils,
alterations in heart rate and respiration, and
urination.
A few people may experience sexual arousal, penile erection, and orgasm.

14. 2. Complex partial seizures
A complex partial seizure often occurs after a simple partial seizure originating in the temporal lobe ►spreads to both temporal lobes in the brain.
A complex partial seizure usually lasts about two to four minutes
A complex partial seizure does not involve convulsions, but it impairs consciousness.
During the seizure, the person will no longer respond to questions.
Someone experiencing a complex partial seizure may become
frightened and
try to run and struggle.
Following the seizure, there will be no memory of it.
During a complex partial seizure, the person stops and has a blank look or empty stare.
S/he will appear unaware of the environment and may seem dazed مصاب بدوار.

15. The seizure may progress to manifest any of the following “inappropriate” automatic behaviors (automatisms are not always present): chewing movements uncoordinated activity meaningless bits of behavior that appear random and clumsy including picking at their clothes or trying to remove them walking about aimlessly picking up things mumbling تمتمة After the seizure, there is usually a period of confusion lasting longer. Once the pattern of seizures is established, it will usually be repeated with each subsequent seizure

16. 2. Generalized Seizures
Generalized epileptic seizures are characterized by diffuse, excessive, and uncontrolled neuronal discharges that at the outset spread rapidly and simultaneously to both cere­bral hemispheres through interconnections between the thalamus and cortex.
However, it is some­times difficult clinically to distinguish between a primary generalized seizure and a focal seizure that rapidly spreads.
Generalized seizures are subdivided primarily on the basis of the ictal motor manifestations, which, in turn, depend on the extent to which subcortical and brain stem regions participate in the seizure.
Generalized Tonic-Clonic (Grand Mal) Seizures)
1. Tonic-clonic: Characterized by:
The duration of the seizure is usually 1 to 3 minutes.
These seizures are often described as “grand mal.”
The seizures are divided into two phases, the tonic phase and the clonic phase, hence the name of the seizure, though a tonic–clonic seizure will often be preceded by an aura.

17. Aura
An aura for some people, is the first symptom of a seizure
An aura is a form of simple partial seizure
An aura is experienced as peculiar sensory or motor phenomenon.
Common aura descriptions:
butterflies in the stomach, you are very nervous or excited about something.
flashes of light,
odd noises (e.g. buzzing in the ear),
strange smells (e.g. burnt toast, rotten eggs),
 a powerful emotion, dizziness
An aura may last as little as a few minutes or as long as several hours, though some with epilepsy do not experience them at all. Many auras are followed by a tonic–clonic seizure.
Tonic phase
The person will quickly lose consciousness,
the skeletal muscles will suddenly tense, often causing the extremities to be pulled towards the body or rigidly pushed away from it, which will cause the person to fall if standing.
The tonic phase is usually the shortest part of the seizure, usually lasting only a few seconds. The person may also express vocalizations like a loud moan or scream during the tonic stage, due to air forcefully expelled from the lungs.

18. Clonic phase
The person's muscles will start to contract and relax rapidly, causing convulsions. These may range from exaggerated twitches of the limbs to violent shaking or vibrating of the stiffened extremities.
The person may roll and stretch as the seizure spreads.
The eyes typically roll back or close
the tongue often suffers bruising sustained by strong jaw contractions.
The typical EEG from almost any region of the cortex during the tonic phase of generalized tonic-clonic seizure demon­strates that
high-voltage, high-frequency discharges occur over the entire cortex; on both sides of the brain at the same time, demonstrating that the abnormal neuronal circuitry responsible for the attack strongly involves the basal regions of the brain that drive the two halves of the cerebrum simultaneously.

19. What Initiates a Generalized Tonic-Clonic Seizure
What Initiates a Generalized Tonic-Clonic Seizure? The majority of generalized seizures are idiopathic, which means that the cause is unknown. Many people who have generalized tonic-clonic attacks have a hereditary predis­position to epilepsy, a predisposition that occurs in about 1 of every 50 to 100 persons. In these people, factors that can increase the excitability of the abnormal “epilepto­genic” circuitry enough to precipitate attacks include (1) strong emotional stimuli, (2) alkalosis caused by over ­breathing (3) drugs, (4) fever, and (5) loud noises or flash­ing lights. Even in people who are not genetically predisposed, certain types of traumatic lesions in almost any part of the brain can cause excess excitability of local brain areas, as we discuss shortly; these local brain areas also sometimes transmit signals into the activating systems of the brain to elicit tonic-clonic seizures. What Stops the Generalized Tonic-Clonic Attack? The extreme neuronal over activity during a tonic- clonic attack is presumed to be caused by massive simultaneous activa­tion of many reverberating neuronal pathways throughout the brain. Although the factors that terminate the attack are not well understood, it is likely that active inhibition occurs by inhibitory neurons that have been activated by the attack.

20. Absence Seizures (formerly called Petit Mal Seizures) Absence seizures usual course begin in childhood or early adolescence and then to disappear by the age of 30 years. On occasion, an absence seizure will initiate a generalized tonic-clonic (grand mal) attack. Absence seizures account for 15 to 20 percent of epilepsy cases in children. Absence sei­zures almost certainly involve the thalamo-cortical brain activating system. Absence seizures usually characterized by 3 to 30 seconds of unconsciousness or diminished consciousness, during which time the person often stares and has twitch-­like contractions of muscles, usually in the head region, especially blinking of the eyes; ▼ this phase is followed by a rapid return of consciousness and resumption of previous activities. This total sequence is called the absence syn­drome or absence epilepsy. Absence sei­zures patient may have one such attack in many months or, in rare instances, may have a rapid series of attacks, one after the other. Absence sei­zures brain wave pattern is demonstrated by the middle recording which is typified by a spike and dome pattern. The spike and dome can be recorded over most or all of the cerebral cortex, showing that the seizure involves much or most of the thalamocortical activating system of the brain. In fact, animal studies suggest that it results from oscilla­tion of (1) inhibitory thalamic reticular neurons (which are inhibitory gamma-aminobutyric acid [GABA]-producing neurons) (2) excitatory thalamocortical and cortico­thalamic neurons.

21. 3. Myoclonic(infantile spasm):
Seen in children or infants, caused by cerebral pathology, often with mental retardation
Infantile spasms usually disappear by age 4, but child may develop other types of seizures.
Characterized by:
A. Single and very brief jerks of all major muscle groups. It is of two types:
Extensor type – infant extends head, spreads arms out, bend body backward in “spread eagle” position.
Mixed flexor and extensor types may occur in clusters or alternate.
B. May cause children to drop or throw something.
C. Infant may cry out, grunt القُباع وهو صوت الخنزير, grimace يكشِّر أو يلوي قسمات وجهة لإضحاك الآخرين, laugh, or appear fearful during an attack.
D. Patients with these may not lose consciousness, due to the seizure lasting less than 3 to 4 seconds.
E. Patients may describe these seizures as shoulder shrugs or spinal chills.
F. Myoclonic seizures may cluster and build into a generalized tonic-clonic seizure.
G. Myoclonic type is often transient may occur repetitively.

22. 4. Atonic:
Characterized by:
A. The patient loses consciousness and muscle tone.
B. No muscle movements are typically noted, and the patient will fall when they are not lying down or sitting in a chair.
C. These seizures may be described as “falling out.”
D. Usually occurring in children, this type is associated with complete loss of consciousness and muscle tone.