EPILEPSY PATHOPHYSIOLOGY B.PHARM 2ND SEM.pptx

EPILEPSY

1. EPILEPSY SUBHAM SOURAJIT M.PHARM (PHARMACOLOGY) ASST. PROFESSOR JEYPORE COLLEGE OF PHARMACY

2. introduction Epilepsy is a neurological disorder which shows the unpredictable occurrences of seizures which can appear periodically and these seizures get temporarily resolved (spontaneously). The person may become unconscious during these seizures. The duration of these seizures lasts about 2 -5 minutes. Epileptogenesis is the gradual process by which a normal brain develops epilepsy. Most of the cases of epilepsy remain idiopathic (unknown reason). But some cases involves brain injury, stroke, brain tumors , infections of the brain, and birth defects as cause of epileptogenesis . Small number of population gets affected due to genetic mutations. Epileptic seizures are the result of excessive and abnormal neuronal activity in the cortex of the brain.

3. TYPES OF SEIZURES A) Partial seizures This type is characterized by the local effects i.e seizures start at particular area and remain confined to that area only. This occurs mainly due to lesions or disease to the particular part of the brain. This may or may not cause loss of consciousness (depends on type). It can be subdivided as: i ) Simple partial seizures -- It involves repeated involuntary muscle contractions limited to single limb. The duration of these seizures is around 30-60 seconds. Consciousness is not lost. Hallucinations, excessive sweating, dilation of pupils can occur. ii) Complex partial seizures -- Duration of these seizures is around 2-5 minutes. The characteristic features include impaired consciousness and automatism. (automatism refers to purposeless movements, emotional changes, walking etc.) iii) Partial seizures evolving to generalized seizures -- The partial seizures progresses to tonic- clonic seizures.

4. B) Generalized seizures It is characterized by abnormal firing of neurons (excessive electrical discharges). Patient becomes unconscious. i ) Absence seizures -- In an absence seizure, epileptic activity occurs throughout the entire brain. It is a milder type of epilepsy that causes unconsciousness without convulsions. After the seizure, the person has no memory of it. Ongoing activities get stopped. Posture is not lost and its duration is around 2-10 seconds. Formerly it is called as petitmal . ii) Tonic clonic seizures -- Also called as grandmal seizures. During a generalized tonic- clonic (formerly grand mal) seizure, electric discharges originate at small area of brain and spread toentire brain. Temporary loss of consciousness occurs. A tonic- clonic seizure usually lasts one to three minutes, but may last up to five minutes. Muscles get stiffen (muscle spasm) and person get fallen on the ground. iii) Myoclonic seizures -- This involves jurking of muscles in part or all of the body. A hand may suddenly fling out, a shoulder may shrug, a foot may kick, or the entire body may jerk. iv ) Clonic seizures- - a person may lose control of bodily functions and begin During a clonic seizure, jerking in various parts of the body. He/She may temporarily lose consciousness, followed by confusion. v) Tonic seizures -- In this type tone is greatly increased. The body, arms, legs suddenly become stiff or tense. Person may aware or slight change of awareness may occur.

5. TYPES OF EPILEPSY A) On the basis of intensity of seizures i ) Grandmal epilepsy (see tonic clonicseiaures ) ii) Petitmal epilepsy (See absence seizures) B) Other types: i ) Juvenile myoclonic epilepsy ( Janz syndrome) -- 5 -10 % cases are found with this type of epilepsy amongst total epileptic cases. It occurs in age groups of 8 -20 years. ii) Benign partial epilepsy in childhood -- It occurs in patients below 12 years. It starts with partial seizures which may progress into generalized tonic- clonic seizures. iii) Solitary parenchymal cysts -- Single small cyst (dormant stage of microbs ) if present in nervous system it causes infection known as neurocysticercosis . iv) Reflex epilepsy -- The specific event or action becomes responsible for attack of epilepsy like photosensitivity, hot water, cold water, visual stimuli.

6. STATUS EPILEPTICUS It is characterized by the occurance of repeated seizures without full recovery from unconsciousness between the seizures. The duration of seizure may be from 5 minutes to 30 minutes. Generally tonic clonic seizure occurs rarely absence or partial complex seizures may occur.

7. PATHOGENESIS The misbalancing in following neurotransmitters may be involved in development of epilepsy: Gamma Amino Butyric Acid (GABA)is a inhibitory neurotransmitter it reduces the neuronal excitation. Glutamate neurotransmitters and receptors For these transmitters there are two receptors are present in central nervous systemi.e . NMDA (N-methyl-D- aspartate ) and nNMDA . NMDA is responsible for neuronal excitation and nNMDA is responsible for inhibition of neuronal activity. NMDA receptors generally modulate Ca+ and Na+ channels opening of which causes excitation of neurons

8. CAUSES OF EPILEPSY For about 25% of cases cause is known but for rest of 75% cases does not show any reason i.e. they are idiopathic. Genetic influence -- Some cases shows genetic influence. In most of the cases genes are not directly involve in generation of seizures but they increase the risk of attack of seizures. Certain genes may make a person more sensitive to environmental conditions that trigger seizures. Head trauma -- Head trauma as a result of a accident or other traumatic injury can cause epilepsy. Brain status -- Brain conditions that cause damage to the brain, such as brain tumors or strokes , 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.

9. Developmental disorders -- Epilepsy can sometimes be associated with developmental disorders, such as autism and neurofibromatosis . Risk factors -- Certain factors may increase risk of epilepsy : Age -- The onset of epilepsy is most common in children and older adults, but the condition can occur at any age . Family history -- If you have a family history of epilepsy, you may be at an increased risk of developing a seizure disorder. Head injuries -- Head injuries are responsible for some cases of epilepsy. You can reduce your risk by wearing a seat belt while riding in a car and by wearing a helmet while bicycling, skiing, riding a motorcycle or engaging in other activities with a high risk of head injury. Dementia -- Dementia can increase the risk of epilepsy in older adults. Brain infections -- Infections such as meningitis, which causes inflammation in your brain or spinal cord, can increase your risk. Seizures in childhood -- High fevers in childhood can sometimes be associated with seizures. Children who have seizures due to high fevers generally won't develop epilepsy. The risk of epilepsy increases if a child has a long seizure, another nervous system condition or a family history of epilepsy.

10. COMPLICATIONS A) Complications of complex partial seizures are easily triggered by emotional stress. The limbic structures ( i.e ., hypothalamus, hippocampus, amygdala ) of the brain may be damaged by seizure activity. The limbic system is concerned with emotion and motivation. These patients may develop cognitive and behavioral difficulties, such as the following: Interictal personality: humorlessness, dependence, obsessions, anger, hypo- or hypersexuality , emotionality. Memory loss: short-term memory loss attributable to dysfunction in the hippocampus, anemia (inability to recall words or names of objects). Poriomania : prolonged aimless wandering followed by amnesia. Violent behavior : aggression and defensiveness when subjected to restraint during a seizure. B) Complications associated with tonic- clonic seizures may involve injury, such as the following: Aspiration (inhalation into the lungs) of secretions or vomited stomach contents. Skull or vertebral fractures, shoulder dislocation. Tongue , lip, or cheek injuries caused by biting. Status epilepticus .

11. MEDICATIONS Voltage dependent ion channels– Carbamazepine , Valporic Acid. GABA– Phenobarbitol , Benzodiazepine. Suppression of excitory neuro transmission– Lamotrigine .