Mariano Marcos State University

COLLEGE OF HEALTH SCIENCES Department of Pharmacy City of Batac

EPILEPSY
(CASE STUDY) In partial fulfillment of the requirements in Pcare 105

ARELLANO, MENARD B. BULAN, NIKKO ANGELO M. DOMINGO, ALFREDO D. JR.

Group X BPh IV-B

I.

Review of the Anatomy of the System

NERVOUS SYSTEM Nervous system is the master controlling and communicating system in the body. Every thought, action, and emotion reflects its activity. Its signaling devices, or means of communicating with body cells, is electrical impulses, which are rapid and specific and cause almost immediate responses. To carry out its normal role, the nervous system has three overlapping functions. (1) Much like a sentry, its uses its millions of sensory receptors to monitor changes occurring both inside and outside the body. This changes are called

stimuli, and the gathered information is called sensory input. (2) Its processes and interprets the sensory input and decides what should be done at each momenta process called integration. (3) It then effects a response by activating muscles or glands (effectors) via motor output. The nervous system does not work alone to regulate and maintain body homeostasis; the endocrine system is a second important regulating system. Whereas the nervous system controls with rapid electrical nerve impulses, the endocrine system typically brings about its effects in a more leisurely way. 1. Structural Classification a. Central Nervous System (CNS) Central nervous system (CNS) consists of the brain and the spinal cord, which occupy the dorsal body cavity and acts the integrating and command centers of the nervous system. They interprets incoming sensory information and issue instruction based on past experience and current condition.

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Brain The adult brains unimpressive appearance gives few hints in its remarkable abilities. It is about two good fistfuls of pinkish gray tissue, wrinkled like a walnut and with the texture of cold oatmeal. It weighs a little over three pounds. Because the brain is the largest and most complex mass of nervous tissue in the body, it is commonly discussed in terms of its four major regions.

 Cerebral hemispheres: the paired cerebral hemisphere, collectively called the cerebrum, are the most superior part of the brain and together are a good deal larger than the other three brain regions combined. The entire surface cerebral hemispheres exhibits elevated ridges of tissue called gyri, separated by swallow grooves called sulci. Each cerebral hemisphere has three basic regions: a superficial cortex of gray matter, which looks gray in fresh brain tissue; an internal white matter and the basal nuclei, island of the gray matter situated deep within the white matter.  Cerebral cortex: speech, memory, logical and emotional response, as well as consciousness, interpretation of sensation, and voluntary movement, are all function of neurons of the cerebral cortex. The primary somatic sensory area is located in the parietal lobe posterior to the central sulcus. The primary motor area, which allows us to consciously move our skeletal muscle, is anterior to the central sulcus in the frontal lobe. A specialized cortical area that is very involved in our ability to speak, Brocas area, is found in the base in the pre-central gyrus. The speech area is located in the junction of the temporal, parietal, and occipital lobe.  Cerebral white matter: is composed of fiber tracts carrying impulses to, from, of within the cortex. One very large fiber tract, the corpus callosum, connects the cerebral hemisphere. Such fiber tracts called commisures. The corpus callosum arches above the structure of the brain stem and allows the cerebral hemisphere to communicate with one another.  Basal nuclei: although most of the gray matter is in the cerebral cortex, there are several island of gray matter, called the basal nuclei, or basal ganglia, buried deep within the white matter of the cerebral hemisphere. The basal nuclei help regulate voluntary motor activities by modifying instructions sent to the skeletal muscles by the primary motor cortex. ii. Diencephalon The diencephalon, or the interbrain, sits atop the brain stem and is enclosed by the cerebral hemisphere. The major structures of the diencephalon are the thalamus, hypothalamus, and epithalamus.

 Thalamus: which enclosed the swallow third ventricle of the brain, is a relay station for the sensory impulses passing upward the sensory cortex.  Hypothalamus: it is an important autonomic nervous system center because it plays a role in the regulation of body temperature, water balance and metabolism. The hypothalamus is also center for many drives and emotions, and as such it is an important part of the socalled limbic system. The pituitary gland hangs from the anterior floor of the hypothalamus by a slender stalk. The mammillary bodies, reflex centers involved in olfaction, bulge from the floor of the hypothalamus posterior to the pituitary gland.  Epithalamus: forms the roof of the third ventricle. Important part of the epithalamus are the pineal body and the choroid plexus of the third ventricle. The choroid plexus, knots of capillaries within each ventricles, form the cerebrospinal fluid. iii. Brain Stem The brain stem is about the size of a thumb in diameter and approximately 3 inches(approximately 7.5 cm) long. Its structure are the midbrain, pons and medulla oblongata.  Midbrain: the midbrain is relatively small part of the brain stem. It extends from the mammillary bodies to the pons inferiorly. The cerebral aqueduct is a tiny canal that travels through the midbrain and connects the third ventricle of the diencephalon to the fourth ventricle below. The midbrain is composed primary of two bulging fiber tracts, the cerebral peduncles, which convey ascending and descending impulses.  Pons: the pons is the rounded structure that produce just below the midbrain. Pons means bridge and this area of the brain stem is the mostly fiber tracts.  Medulla oblongata: the medulla oblongata is the most inferior part of the brain stem. It merge into the spinal cord below without any obvious change in the structure. The medulla also contains many nuclei that regulate vital visceral activities.

 Reticular formation: extending the entire length of the brain stem is a diffuse mass gray matter. The neurons of the reticular formation are involved in the motor control of the visceral organs. A special group of reticular formation neurons, the reticular activating system (RAS), plays a role in consciousness and the awake/sleep cycles. Damage to this area can result in permanent unconsciousness. iv. Cerebellum The large cauliflower-like cerebellum projects dorsally from under the occipital lobe of the cerebrum, the cerebellum has two hemispheres and a convoluted surface. The cerebellum also has an outer cortex made up gray matter and an inner region of white matter. Cerebrospinal fluid The cerebrospinal fluid (CSF) is a watery broth similar in its makeup to blood plasma, from which is forms. CSF is continually formed from the blood by the choroid plexuses. Choroid plexuses are clusters of capillaries hanging from the roof in each of the brains ventricles. The CSF in and around the brain and cord forms a watery cushion that protects the fragile nervous tissue from blows and other trauma.

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Spinal Cord The cylindrical spinal cord, which is approximately17 inches (42 cm) long and, is a glistening white continuation of the brain stem. The spinal cords provides a two-way conduction pathway to and from the brain, and it is a major reflex center. Enclosed within the vertebral column, the spinal cord extends from the foramen magnum of the skull to the first or second lumbar vertebra. Where it ends just below the ribs. In humans, 31 pairs of spinal nerves arise from the cord and exit from the vertebral column to serve the body area and close by.  Gray matter of the spinal cord and spinal roots The gray matter of the spinal cord looks like a butterfly or a letter H in cross section. The posterior projections are the dorsal, or posterior, horns; the two anterior projection are the ventral, or anterior, horns. The gray matter surrounds the central canal of the cord which contains CSF.

 White matter of the spinal cord The white matter of the spinal cord is composed of myelinated fibers tractssome running to higher center, some traveling from the brain to the cord, and some conducting impulses from one side of the spinal cord and other. b. Peripheral Nervous System (PNS) Peripheral nervous system (PNS), the part of the nervous system outside the CNS, consists mainly of the nerves that extend from the brain to the spinal cord. Spinal nerves carry impulses to and from the spinal cord. Cranial nerves carry impulses to and from the brain. These nerves serves as communicating lines. They link all parts of the body by carrying impulses from the sensory receptors to the CNS and from the CNS to the appropriate glands or muscle. i. Nerve A nerve is a bundle of neuron fibers found outside the CNS. Within a nerve, neuron fibers, or processes, are wrapped in protective connective tissue coverings. Each fiber is surrounded by a delicate connective tissue sheath, an endoneurium. Groups of fibers are bound by a coarser connective tissue wrapping. The perinurium, to form fiber bundles, or fascicle. Finally, all the fascicles are bound together by a tough fibrous sheath, the epineurium, to form the cordlike nerve. Cranial Nerve The 12 pairs of cranial nerves primarily serves the head and neck. Only one pair extends the thoracic and abdominal cavities. The cranial nerves are numbered in order, and in most cases their names their reveal the most important structures they control. Spinal Nerves and Nerve Plexuses The 31 pairs of human spinal nerves are formed by the combination of the ventral and dorsal roots of the spinal cord. Each spinal nerve and divides into dorsal and ventral rami, making each spinal nerve only about inch long. The rami, like the spinal nerves contain both motor and sensory fiber.

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2. Functional Classification a. Sensory or Afferent Division Consists of nerves (composed of nerve fibers) that convey impulses to the central nervous system from sensory receptors located in various

parts of the body. Sensory fibers delivering impulses from the skin, skeletal muscle, and joints are called somatic (soma = body) sensory (afferent) fibers, whereas those transmitting impulses from the visceral organs are called visceral sensory fibers, or visceral afferents. These sensory division keeps the CNS constantly informed of events going on both inside and outside the body. b. Motor or Efferent Divisions Motor or efferent divisions carries impulses from the CNS to effector organs, the muscle and glands. These impulses activate muscle and glands; that is, they effect a motor responses. i. Somatic nervous system allows us to consciously, or voluntarily, control our skeletal muscle. Hence, this subdivision is often referred to as the voluntary nervous system. However , not all skeletal muscle activity controlled by this motor division is voluntary. Autonomic nervous system (ANS) regulates events that are automatic, or involuntary, such as the activity of smooth and cardiac muscle and glands. This subdivision, commonly called involuntary nervous system, itself has two parts, the sympathetic and parasympathetic, which typically bring about opposite effects. What one stimulates and other inhibits.

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3. Nervous Tissue a. Supporting Cells Supporting cells in the CNS are lumped together as neuroglia, literally, nerve glue. Neuroglia includes many types `of cells that generally support, insulate and protect the delicate neurons. Each of the different types of neuroglia, also simply called either glia or glial cells. i. Astrocyets: abundant star-shaped cells that account for nearly half of the neural tissue. Their numerous projections have swollen ends that cling of neurons, bracing then and anchoring them to their nutrient supply lines, the blood capillaries. Astrocytes also help control the environment in the brain by mopping up leaked ions and recapturing released neurotransmitters. Microglia: spiderlike phagocytes that dispose of debris, including dead brain cells and bacteria.

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iii.

Ependymal cells: these glial cells line the central cavities of the brain and the spinal cord. The beating their cilia helps to circulate the cerebrospinal fluid that fills those cavities and forms a protective cushion around the CNS. Oligodendrocytes: glial that wrap their flat extensions tightly around the nerve fibers, producing fatty insulating coverings called myelin sheath.

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b. Neurons Neurons, also called nerve cells, are highly specialized to transmitted message (nerve impulses) from one part of the body to another. i. Cell body is the metabolic center of neuron. Its transparent nucleus contains a conspicuous nucleolus. The cytoplasm surrounding the nucleus contains the usual organelles except for centroiles. The rough ER, called Nissl substance, and neurofibrils (intermediate filaments that are important in maintaining cell shape) are particularly abundant in the cell body. Processes the armlike processes, or fibers vary in length from microscopic to 3 to 4 feet. Neuron processes that convey incoming messages toward the cell body are dendrites, whereas those that generates nerve impulses and typically conduct them away from the cell body are axons. Each axon terminal is separated from the next neuron y a tiny gap called synaptic cleft. Such a functional junction called a synapse (syn = to clasp or join). Myelin sheath most long nerve fibers are covered with a whitish, fatty material, which has a waxy appearance. Myelin protects and insulates the fibers and increase the transmission rate of nerve impulses. Axons outside the CNS are myelinated by Schwann cells. This part of the Schwann cell, external to the myelin sheath, is called the neurilemma. Because the myelin sheath is formed by many individual Schwann cells, it has gaps, or indentations called nodes of Ranvier at regular intervals.

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Definition of Disease Seizure Seizure is the physical findings or changes in behavior that occur after an episode of abnormal electrical activity in the brain. The term "seizure" is often used interchangeably with "convulsion." Convulsions are when a person's body shakes rapidly and uncontrollably. During convulsions, the person's muscles contract and relax repeatedly. There are many different types of seizures. Some have mild symptoms and no body shaking. Types of seizure 1. Generalized Seizure There are six types of generalized seizures. The most common and dramatic, and therefore the most well known, is the generalized convulsion, also called the grand-mal seizure. In this type of seizure, the patient loses consciousness and usually collapses. The loss of consciousness is followed by generalized body stiffening (called the "tonic" phase of the seizure) for 30 to 60 seconds, then by violent jerking (the "clonic" phase) for 30 to 60 seconds, after which the patient goes into a deep sleep (the "postictal" or after-seizure phase). During grand-mal seizures, injuries and accidents may occur, such as tongue biting and urinary incontinence.  Absence seizures cause a short loss of consciousness (just a few seconds) with few or no symptoms. The patient, most often a child, typically interrupts an activity and stares blankly. These seizures begin and end abruptly and may occur several times a day. Patients are usually not aware that they are having a seizure, except that they may be aware of "losing time."  Myoclonic seizures consist of sporadic jerks, usually on both sides of the body. Patients sometimes describe the jerks as brief electrical shocks. When violent, these seizures may result in dropping or involuntarily throwing objects.  Clonic seizures are repetitive, rhythmic jerks that involve both sides of the body at the same time.  Tonic seizures are characterized by stiffening of the muscles.

 Atonic seizures consist of a sudden and general loss of muscle tone, particularly in the arms and legs, which often results in a fall. 2. Partial Seizures Partial seizures are divided into simple, complex and those that evolve into secondary generalized seizures. The difference between simple and complex seizures is that during simple partial seizures, patients retain awareness; during complex partial seizures, they lose awareness.  Simple partial seizures are further subdivided into four categories according to the nature of their symptoms: motor, autonomic, sensory, or psychological. Motor symptoms include movements such as jerking and stiffening. Sensory symptoms caused by seizures involve unusual sensations affecting any of the five senses (vision, hearing, smell, taste, or touch). When simple partial seizures cause sensory symptoms only (and not motor symptoms), they are called "auras."  Complex partial seizures, by definition, include impairment of awareness. Patients seem to be "out of touch," "out of it," or "staring into space" during these seizures. There may also be some "complex" symptoms called automatisms. Automatisms consist of involuntary but coordinated movements that tend to be purposeless and repetitive. Common automatisms include lip smacking, chewing, fidgeting, and walking. II. Etiology Epilepsy is a chronic disorder surrounded by many myths and misconceptions. Recent advances in the understanding and treatment of epilepsy have improved societal attitudes toward this condition, but the diagnosis still represents the social stigma for many patients. A seizure is an abnormal, paroxysmal electrical discharge from the cerebral cortex, and epilepsy is defined as recurrent, stereotypic seizures. Seizures are seen clinically as alteration of sensation, behavior, movement, perception, or consciousness. Symptoms are related to the area of cortex involved. Any condition that causes cerebral irritation or alters the biochemical environment of the brain can result in seizures. The risk of having an isolated seizure during ones lifetime is thought to be about 10%. Seizure can occur inas a result of a wide range of metabolic derangement that affect the nervous

system; if the underlying condition is corrected, the condition do not recur. These episodic seizures are not the same as epilepsy. An estimated 2 million people in the United States have epilepsy, and approximately 125,000 new cases are diagnosed each year. Thirty percent of newly diagnosed patients are under 18 years old of age. The prevalence of epilepsy in persons over 65 years of age is 1%. When no identifiable cause for epilepsy can be found, the seizure considered idiopathic; idiopathic epilepsy accounts for 70% of all cases. Genetics clearly plays a role in a some forms of epilepsy. The remaining 30% of cases are related to a known cases, such as structure lesions in the central nervous system. Risk factors for developing in adulthood include lesions within the central nervous system, meningitis or encephalitis, cerebral tumors and stroke. Initial seizures in children are often fever, anoxia, cerebral plasy, perinatal problems, congenital central nervous system defects, mental retardation, febrile conditions, family history of epilepsy, head trauma, central nervous system infections, central nervous system tumors, cerebrovascular disease, alcohol or drug abuse, metabolic disturbances, exposure to toxins and degenerative disease. III. Pathophysiology A seizure can be caused by any process thats disrupts the cell membrane stability of neurons. A seizure starts when a tiny cluster of the brain cells begin to emit rapid, repetitive, highly synchronized electrical discharge. The discharge may remain localized or rapidly spread to involved the entire brain. The point at which the cell membrane becomes destabilized and uncontrollable electrical discharge begins its known as seizure threshold. Some people have lower seizure thresholds than others and are therefore more prone to seizures. In 1981 the International League Against Epilepsy proposed a revised classification of seizure. The major categorize are partial (focal) and generalized seizures. Further subdivisions within the categories are based on the persons clinical behavior during the ictal and interictal times. Ictal refers to the time during a seizure. Interictal refers to the time between seizure activity. Postictal refers to the time immediately after a seizure as a patient recovers. Partial seizures do not always affect consciousness. Simple partial seizures have less motor, sensory, and consciousness involvement because they are limited to a smaller area of the brain. The wider the area of cerebral cortex affected, the more clinical symptoms are seen. With simple partial seizures a patient may experience uncontrolled movement of an extremity or a portion of the face. He or she is able to interact with others during the seizure and remembers the event afterwards. Complex partial seizures affect consciousness. Patients may recall an aura, a warning sensation can occurs before the seizure,

and often exhibits automatism, such as lip smacking, chewing , rubbing or picking at clothes. The behaviors are not voluntary because consciousness is impaired. Some complex partial seizures spread to a large areas of the cortex and become generalized tonic-clonic seizures, but these are different from true tonic-clonic seizures, in which the initial seizure behavior is generalized. Generalized seizures impair consciousness from the start. Absence seizures do not include motor signs and may last less than 1 minute. These seizure are often seen in children and may initially be thought of as day dreaming. There is no postictal state, and absence seizure can occur many times a day. Toni-clonic seizures have a tonic phase, during which the muscles become rigid, and then a clonic phase, which involves rhythmic muscle jerking. As a muscle of the trunk and diaphragm become rigid, the air moving past the vocal creates a cry. Once the diaphragm is constructed, the patients is unable to breath. If the seizure lasts long enough, the patient may become cyanotic. Bladder and bowel muscles are also affected, and the patient may experience incontinence. Other generalized seizure include myoclonic and atonic types. Myoclonic seizures cause one or several muscle jerk, often causing the patient to fall. Atonic seizures cause a brief loss of tone in one or more muscle, causing the patient to drop things or fall. They cause only a brief loss of consciousness and no postictal state. The patient is able to get up right away unless he/she is injured in the fall. A seizure is not generally fatal but creates a risk for injury from falls and other environmental problems. Postictal state represents periods of recovery from the seizure. The brain must recover from the intense burst of electrical activity. The length of the postictal period varies from patient to patient. Patient may have some degree of confusion, lethargy, or an inability to follow commands or speak clearly during this period. In cases the patient may experience Todds paralysis, which is prolonged weakness involving one or more extremities. Although not permanent, the paralysis may persist beyond the postictal period of confusion or fatigue. Status epilepticus is an episode of seizure activity lasting at least 30 minutes, or repeated seizures without full recovery between each seizure. Seizures cause a marked increase in cerebral metabolic activity and demands. Oxygen consumption typically increases by 60 % and cerebral blood flow by as much as 250%. These demands may outpace the delivery of oxygen and nutrients from the cerebral blood flow, and prolonged seizures can lead to cellular exhaustion and destruction and even death if not effectively interrupted.

IV.

Clinical Features/Signs and Symptoms The two categories of seizures are generalized and partial. a. Generalized Seizures Generalized seizures are caused by abnormal electrical impulses in the brain and typically occur with no warning. There are six types of generalized seizures.  Tonic-clonic (grand-mal) Seizure This seizure causes you to lose consciousness and often collapse. Your body becomes stiff during what's called the "tonic" phase. During the "clonic" phase, muscle contractions cause your body to jerk. Your jaws clamp shut and you may bite your tongue. Your bladder may contract and cause you to urinate. After one to two minutes, you fall into a deep sleep.  Absence (petit mal) Seizuure During these brief episodes, you lose awareness and stare blankly. Usually, there are no other symptoms. They tend to begin and end suddenly and last for about 10 seconds, although they can last as long as 20 seconds. These seizures may occur several times a day.  Myoclonic Seizure These very brief seizures cause your body to jerk, as if shocked by electricity, for a second or two. The jerks can range from a single muscle jerking to involvement of the entire body.  Clonic Seizure This seizure cause rhythmic jerking motions of the arms and legs, sometimes on both sides of your body.  Tonic Seizure Tonic seizures cause your muscles to suddenly stiffen, sometimes for as long as 20 seconds. If you're standing, you'll typically fall.  Akinetic or Atonic Seizure This seizure causes your muscles to relax or lose strength, particularly in the arms and legs. Although you usually remain conscious, it can cause you to suddenly fall and frequently causes injuries, such as facial cuts. These seizures also are called "drop attacks." b. Partial Seizures Partial seizures, also known as local or focal seizures, are caused by abnormal electrical activity in a specific, smaller part of the brain. The part of the brain causing the seizure is called the seizure focus. Partial seizures are divided into simple and complex seizures.

Some partial seizures evolve into generalized ones and are called secondarily generalized seizures.  Simple Partial Seizure During these seizures, you remain conscious although some people can't speak or move until the seizure is over. Uncontrolled movements, such as jerking or stiffening, can occur throughout your body. You also may experience emotions such as fear or rage or even joy; and odd sensations, such as ringing sounds or strange smells. In addition, you may experience peculiar memories such as a feeling of "deja-vu." Typically, these seizures last less than two minutes.  Complex Partial Seizure During these seizures, you are not fully conscious and may appear to be in a dreamlike state. Typically, they start with a blank stare. You may involuntarily chew, walk, fidget, or perform other repetitive movements or simple actions, but actions are typically unorganized or confused. These seizures typically last between 30 seconds and two minutes.  Secondarily Generalized Seizure These seizures begin as a partial seizure and develop into generalized ones as the electrical abnormality spreads throughout the brain. When the seizure begins, you may be fully conscious but then lose consciousness and experience convulsions as it develops. V. Clinical Evaluation The developing brain is particularly susceptible to seizures. Diffuse central nervous system pathology or injury in early infancy, when the brain is most vulnerable, may lead to catastrophic epilepsies such as Ohtahara's epileptic encephalopathy and early myoclonic epileptic encephalopathy. These epileptic encephalopathies are difficult to treat and have poor prognoses. As the brain undergoes programmed synaptogenesis, apoptosis, and myelination, the epilepsy phenotypes and electroencephalography (EEG) findings change, producing age-dependent epileptic encephalopathies. Specifically, as they grow older, 40% to 60% of infants with infantile spasms and a concomitant hypsarrhythmia on EEG will develop Lennox-Gastaut syndrome with tonic and atonic seizures, associated with a synchronous, generalized 1.5- to 2-Hz spike and slow wave discharges on EEG. In the context of age-dependent epileptic encephalopathies, as an epilepsy syndrome is evolving, it is often difficult to accurately diagnose the specific epilepsy syndrome in a young child who presents with seizures. It is the clinical evolution of the seizure types and the EEG that helps the clinician make an accurate diagnosis. As more is known about the underlying pathophysiology for the various epilepsy syndromes, not only the clinical picture and EEG but also a genetic blood test will be used to accurately diagnose a specific epilepsy syndrome. A case in point would be severe myoclonic epilepsy of infancy (classically known as Dravet syndrome) and

severe myoclonic epilepsy of infancy-borderland/ borderline, which are associated with specific mutations in the sodium ion channel gene SCN1A. VI. Complications Having a seizure at certain times can lead to circumstances that are dangerous to yourself or others. Hypoxic brain damage and mental retardation may follow repeated seizures. Depression and anxiety may develop. Falling. If you fall during a seizure, you can injure your head or break a bone. Drowning. If you have epilepsy, you're 13 times more likely to drown while swimming or bathing than is the rest of the population because of the possibility of having a seizure while in the water.
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Car accidents. A seizure that causes either loss of awareness or control can be dangerous if you're driving a car or operating other equipment. Many states have driver's-licensing restrictions related to your ability to control seizures and impose a minimum amount of time that you've been seizure-free ranging from three months to two years before you're allowed to drive. Pregnancy complications. Seizures during pregnancy pose dangers to both mother and baby, and certain anti-epileptic medications increase the risk of birth defects. If you have epilepsy and you're considering becoming pregnant, talk to your doctor as you plan your pregnancy. Most women with epilepsy can become pregnant and have a healthy baby. You'll need to be carefully monitored throughout pregnancy, and medications may need to be adjusted. It's very important that you work with your doctor to plan your pregnancy. Emotional health issues. People with epilepsy are more prone to have psychological problems, especially depression, anxiety and, in extreme cases, suicide. This could be due to difficulties dealing with the condition itself as well as medication side effects. Other life-threatening complications from epilepsy are uncommon, but do occur. Status epilepticus. This condition occurs if you're in a state of continuous seizure activity lasting more than five minutes, or you have frequent recurrent seizures without regaining full consciousness in between them. People with status epilepticus have an increased risk of permanent brain damage and death.

Sudden unexplained death in epilepsy (SUDEP). People with poorly controlled epilepsy also have a small risk of sudden unexplained death. Overall, less than 1 in 1,000 people with epilepsy die of SUDEP, but it's more common among people whose seizures aren't controlled by treatment. The risk of SUDEP is particularly elevated when generalized tonic-clonic seizures are frequent, and the risk over a one-year period could be as high as approximately 1 in a hundred people.

VII.

Treatment and Monitoring

Drug Therapy General Classification Sodium channel blocking agents Have the capacity to block sustained high frequency repetitive firing (SRF) of action potentials. This is accomplished by reducing the amplitude of sodium dependent action potentials through an enhancement of steady state inactivation. 1. Phenytoin (Dilantin) A valuable for the treatment of generalized tonic clonic seizure and for the treatment of partial seizures with complex symptoms.

MOA:  Blockade of Sodium channels (use dependent) and inhibition of generation of high frequency repetitive action potentials.  At high concentration reduction in calcium influx responsible for inhibition of secretory processes: release of hormones (ADH, insulin) and neurotransmitters (NE, 5HT). Promotes uptake of dopamine and inhibits MAO activity.  Alters sodium, potassium, calcium conductance, membrane potentials and concentrations of amino acids and neurotransmitters.  Drug interacts with membrane lipids and this promotes stabilization of membrane. Pharmacokinetics:  Absorption: - Absorption is slow but usually complete, primarily in the duodenum. - On IM injection absorption poor.

- Fosphenytoin (more soluble prodrug phosphate ester).  Distribution: - Highly bound (about 90%) to plasma proteins, primarily albumin.  Metabolism and excretion: - Half life 12 36(24) hours with mild therapy and steady state is reached in 5 6 days but with higher levels, it may take 4 6 weeks with half life reaching to 60 hour. - Metabolized in liver to parahydroxyphenyl derivative. - Excreted as glucuronide in bile and urine. Adverse effects:  Acute effects: - Nystagmus - Diplopia reduce dose. - Ataxia - Lethargy, sedation at higher concentration.  Chronic effects: - GIT disturbances nausea, vomiting, epigastric pain, anorexia. - Gingival hyperplasia. - Coarsened facial features - Hirsutism, acne - Megaloblastic anemia - Hemorrhagic disease of new born: hypoprothrombinemia and hemorrhage in new borns of mothers. - Use during pregnancy teratogenic: may produce fetal hydantoin syndrome (hypoplastic phalanges, cleft palate, hare lip, microcephaly) - Peripheral neuropathy depressed tendon reflexes - Endocrine effects:  Osteomalacia with hypocalemia due to altered vitamin D and K metabolism.  Inhibition of release of ADH secretion  Inhibition of insulin secretion  Hypersensitivity or idiosyncratic effects: - Skin rashes, fever, and rarely Steven Johnson syndrome, exfoliative lesion, SLE and fatal hepatic necrosis. - Hematological reactions: neutropenia and leucopenia, thrombocytopenia, and rarely red cell aplasia, agranulocytosis - Lymphadenopathy resembling Hodgkins disease

Drug interaction: - Cimitidine, Chloramphenicol, Disulfiram, Sulthiamine, and Isoniazid. - Carbamazepine - Oral contraceptives, oral anticoagulants 2. Carbamazepine (Tegretol) It become a major drug in the treatment of seizure disorders. An effective agent for the treatment of partial seizures,generalized tonic-clonic seizures and bipolar. MOA:  Blocks Na+ channels, inhibits high frequency repetitive firing of neurons.  It acts presynaptically to decrease synaptic transmission.  Inhibits intake and release of NE, potentiate post synaptic GABA action. Pharmacokinetics:  Slowly but completely absorbed orally (poor water solubility). Available only for oral administration.  75% bound to plasma proteins.  Metabolized by oxidation to an active metabolite (10-11 epoxide). Further metabolism is by conjugation to inactive metabolites.  Initial half-life is 36 hours but decreases on chronic administration to 20 hours due to enzyme induction. Adverse effects:  Dose related: -CNS: diplopia is first symptom of over dose and then ataxia, unsteadiness, and drowsiness appear at the higher concentration. -GIT: mild GI upset vomiting, diarrhea. -Other: water retention and hyponatremia can occur in elderly asit enhances ADH action.  Idiosyncratic reaction: -Erythematous rashes. -blood dyscrasias: fatal aplastic anemia and agranulocytosis; mild persistent leucopenia .

-Hepatic dysfunction.  Teratogenicity: -fetal malformation (neural tube defects) and its combination with valporate double teratogenecity. Drug interactions: - Can induce its own metabolism (autoinduction) - Can induce enzymes that metabolize phenytoin, primidone, Phenobarbital,valproic acid, clonazepam, and ethosuximide, and other drugs the patient may be taking. - Erythromycin and Troleandomycin (macrolide antibiotic) - Cimetidine, Propoxyphene and INH 3. Oxcarbazepine (Trileptal) Chemically and pharmacologically related to carbamazepine, but has much less capacity to induced drug metabolizing enzymes. 4. Lamotrigine (Lamictal) Has a broad spectrum of action and is effective in generalized and partial epilepsies.

MOA:  Acts on Na+ channels, suppresses sustained rapid firing of neurons (voltage and use dependent inactivation of Na+ channels).  Also acts on voltage activated Ca+ channels effective in absence seizures.  Also inhibits release of excitatory amino acids- glutamate. Pharmacokinetics:  absorption from the GIT is almost complete; peak plasma levels achieved in about 2 to 5 hours.  Plasma half-life after a single dose = 24 hours; metabolized primarily by glucoronidation. Adverse Effect:  Concentration dependent -dizziness, headache, diplopia, vertigo, sedation, ataxia. -nausea, vomiting.  Idiosyncracy or hypersensitivity reaction:

-rash, Stevens-johnsons syndrome, toxic epidermal necrolysis, sometimes life threatening dermatitis in pediatric patients. -flulike syndrome: patient should report immediately if flu like symptoms or rash appears. . TOPIRAMATE (Topamax) Substitute monosaccharide, structurally different from other antiepileptics. It is a broad spectrum antiepileptic.Most useful in patients with generalized tonicclonic seizures and those with partial complex seizures. MOA:  Blockade of voltage dependent Na+ Channel- blocks repetitive firing of neurons.  Potentiation of inhibitory GABA responses.  Impairement of glutamate receptor activity, blocking AMPAkainate subtype (s)of glutamate receptors.  Weak inhibitor of carbonic anhydrase. ADVERS EFFECT:  Somnolence, fatigue, dizziness, ataxia, cognitive slowing, weight loss.  Acute myopia and glaucoma- stop.  Urolithiasis  Teratogenic 6. ZONIZAMIDE (Zonegran) Effective in partial complex and generalized tonic-clonic seizure. Also appears to be beneficial in certain myoclonic seizure. Half-life is about 60 hours; requires about 2 weeks achieve steady-state levels. ADVERSE EFFECT:  Cerebellovestibular S/E similar to most AEDs sharing its mechanism of action.  Increase incidence of kidney stone. 7. VALPROIC ACID (Depakene) SODIUM VALPROATE (Depakote) Highly effective against absence seizures and myoclonic seizures. Can be used alone or in combination with other drugs for the treatment generalized tonic-clonic epilepsy and for partial seizures with complex symptoms. Well absorbed the GIT and highly bound to 90% plasma protein.

MOA:  Blockade of voltage activated Na+ channels  Blockade of NMDA receptor mediated excitation.  Increase in GABA content of brain by: - Stimulating the activity of GABA synthetase enzyme, glutamic acid decarboxylase (GAD) enzyme responsible for GABA synthesis. - Inhibits GABA transpoter GATI - At high concentration: inhibit 2 enzyme systems that inactivate GABA namely GABA transaminase and succinic semialdehyde dehydrogenase.  Enhancement of postsynaptic action of GABA  Blockade of low threshold (T) Ca + channels.  Decrease in aspartate levels.  At high concentration increase in K+ ion permeability leading to hyperpolarization. ADVERSE EFFECTS:  Concentration dependent - GIT nausea, vomiting, abdominal pain, heartburn - CNS: sedation, uncommon, may occur when given with phenobarbitone. Fine tremor at high level. - Others:  Alopecia, thinning and curling of hair  Peripheral edema.  Weight gain, increased appetite.  Idiosyncratic reactions - Fatal hepatic failure - Hepatotoxicity - Rashes and thrombocytopenia  Teratogenic (neural tube defects) DRUG INTERACTIONS - Phenobarbital, Phenytoin Drugs that Primarily Enhance the Action of GABA Benzodiazepines Used in the treatment of absence, myoclonic, and atonic seizures and in the emergency treatment of status epilepticus.

MOA  To enhance inhibition through their action with the GABA receptor at the benzodiazepines binding sites.  Additional action: blocking voltage-dependent sodium channels. This effect is not seen at a usual does but is likely a factor in their use in status epilepticus. Benzodiazepines used in seizure disorder 1. Clonazepam The first benzodiazepines approved in the U.S. specially for the treatment of convulsion disorders. Unfortunately, sedation and tolerance tend to limit its usefulness. Drooling and hypersalivation may be troublesome in infants and in children. 2. Lorazepam The benzodiazepines of choice for the emergency treatment of status epilepticus, serial seizures and prolong seizures and for the prophylaxis of febrile seizures. The IV route is preferable for emergency treatment. 3. Clorazepate Dipotassium As an adjunct in the treatment of partial complex seizures; useful especially in patients with high seizure frequencies and psychic disturbances. Adverse effects  Drowsiness, dizziness and lethargy-some tolerance develops on chronic use.  Lac of concentrations, irritability, temper and other behavioral abnormalities in children.  Dose dependent motor disturbance: ataxia, hypotonia, dysarthria.  Salivation and increase respiratory secretions.  Tolerance develops to therapeutics effects in 6 months or so. 4. Tiagabine (Gabitril) An analog of GABA and a derivative of nipecotic acid, lipohilic. Primarily used in the treatment of partial complex seizures. MOA  Blocks the reuptake of GABA into neurons and glia, thereby resulting in higher levels of GABA in the synaptic cleft

Adverse Effects  Dizziness, somnolence, nervousness, nausea and confusion. . Vigabatrin (Sabril) Gamma vinyl GABA derivative. Primary indication in the treatment of partial seizures.

6. Phenobarbital and Primidone Considered as alternative treatment of partial seizures and for generalized tonic-clonic epilepsy (they are judge to be less effective than carbamazepine and phenytoin). MOA  GABA facilitator, GABA-mimeticit acts on GABA receptor and enhances chloride conductance, causes potentiation of synaptic inhibition at the therapeutic concentration.  Antiglutamate-blocks excitatory responses of glutamate.  At higher concentration: Na+ and L, N type calcium channels. Pharmacokinetics  Well absorbed, 50% bound to plasma protein has a long half-life (100 hours, longer in neonate), 75% metabolized in liver by oxidation and conjugation with glucoronide, some (25%) excreted unchanged in urine, which is the pH dependent.  Steady state concentration are reach in 2-3 weeks, a single daily dose is effective.  It is powerful enzyme inducer. Adverse Effects  Sedation tolerance occurs on chronic use.  Nystagmus, ataxia-at high doses.

MOA  A relatively specific irreversible inhibitor of GABA-transaminase (GABA-T) Adverse Effects  Drowsiness, dizziness, weight gain.  Agitation, confusion, and psychosis.  Irreversible visual fields defects.

 Long-term use diminution of intelligence, impairment of learning the memory, impaired school performance, behavioral abnormalities, depression, and mental confusion in elderly.  Megaloblastic anemia and osteomalacia on prolong use.  Hemorrhagic disease of new born  Hypersensitivity reactions: rashes, exfoliative dermatitis, hypoprothrombinemia. Agents That Block T calcium Channels 1. Ethosuximide (Zarontin) Used in the treatment of absence epilepsy. MOA  Reduces the low-threshold calcium current (LTCC) or T (transient) current. These current underlie the 3-Hz spike wave discharges that are characteristics of absence epilepsy. Adverse Effects  Dose related effects: -GI irritation, nausea, vomiting, anorexia -CNS: lethargy, fatigue, sometimes lethargy dizziness, mood changes, agitation, headache, drowsiness, and inability to concentrate.  Idiosyncratic reactions: -Rare, rashes, SJ syndromes -Blood dyscrasias- eosinophilia, lecopenia, pancytopenia. Noncategorized 1. Gabapentine Effective in both types of epilepsy-generalized and partial seizures. As an analgesic for neuropathic pain-post herpetic neuralgia. It also for migraine and bipolar disorder. MOA  Is a highly lipid soluble, amino acid related to GABA, effective against partial seizures.  Alter GABA metabolism- its nonsynaptic release or its reuptake by GABA transporter  Also binds to Ca++ channels. Adverse Effects  Sedation, ataxia, headache and tremor.

Other Therapeutic Measures For some patients, surgery may be recommended to prevent seizures or to implant devices that deliver medications or stimulators to emit electrical impulses. Your neurologist will explain the procedure as well as possible risks.

 Focal Resections The removal of a small area of the brain where seizures

originate. This procedure often results in complete seizure control.

in the brain and triggers epileptic seizures. Two types of disconnection operations are:
o o

Corpus callostomy, which stop atonic and tonic seizures. Multiple subpial transections, which are performed when seizures are caused by parts of the brain that can't be removed.

 Focal Resections These procedures are the most common operations for

treating epilepsy and provide the best chance for patients to gain complete seizure control. They involve the removal of a small area of the brain where seizures originate. New brain monitoring techniques allow doctors to better pinpoint brain tissue causing seizures. Types of resections include:
o

Temporal lobectomy, where a portion of the temporal lobe is removed to control seizures. Lobar resection, where a portion of a seizure-producing lobe frontal, parietal or occipital lobe is removed, if it can be done without damaging vital functions. Hemispherectomy, where one sphere of the brain is removed or disabled. The remaining half of the brain takes over many of the functions of the half that was removed. This procedure is used to treat severe conditions that have not responded to other treatments.

 Gamma Knife Radiosurgery This procedure delivers a finely focused, high dose

of radiation to remove tissue without damaging surrounding tissue. Some types of seizures, such as gelastic seizures which are accompanied by brief, sudden bursts of emotion, can be treated with this technology. Doctors at UCSF Medical Center are involved in research using the Gamma Knife to treat temporal lobe epilepsy.
 Vagus nerve stimulation This procedure involves minor surgery and is a

relatively new treatment that helps prevent or lessen the severity of seizures. An electrical stimulator is implanted that sends regular electrical pulses through the vagus nerve to the brain to reduce the onset or frequency of seizes.

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Patient Case y Patient Information  Name: BUDOY  Address: Brgy.1,Juan Solsona, Ilocos Norte  Hospital Number: 01-13-79  Sex: Male  Age: 16 years old  Place of birth: Manila  Date of Birth: September 17,1986  Civil Status: Single  Religion: Roman Catholic  Educational Attainment: Day care Graduate  Date of admission to the hospital: December 8, 2011 (12:15 AM) Chief-Complaint Five hours prior to admission: two times of watery stool, five times of vomiting of previous ingested food and abdominal pain. History of Present Illness Budoy is positive in epilepsy and maintain in Phenobarbital and positive in cerebral pulsy. At the age of 10 he has a cerebral hypoxia and started taking Phenobarbital up to the present. Epilepsy mostly attack every month 7-8 times usually at night. Past Medical History Budoy was describe as yellow baby at the age of 7 days old. At the age of 10, budoy has a cerebral hypoxia and started a cough and fever with associated vomiting at the age of 12. Social History Budoy drink 7-8 cup of coffee everyday. He started drinking coffee when he was 14 years old. He eats a lot of vegetable and fish as his primary meal. For the past 6 years, he takes tiki-tiki as vitamins when he was a child. He started to walk at the age of 7 and started to talk at the age of 10. He loves listening music as loud as he wanted and play with his childhood neighbors as his recreational activity. He doesnt smoke and drink beverages, in fact he doesnt have any vices except drinking coffee everyday. He is an undergraduate in elementary and he lives with his auntie and cousins in a simple house.

Family History Budoys mother is a lady guard and still alive at the age of 39 and lives in Ilo-ilo. Together with her mother, Budoys father is still alive at the age of 57 and lives with his wife in Ilo-ilo. Budoy has 3 sisters and they live with their parents in ilo-ilo. Budoy is the eldest among his siblings. He was adopted by his auntie since he was 7 month old and migrated in Barngay 1 Juan, Solsona, Ilocos Norte where he was raised by his relatives. His grandmother was diagnosed of epilepsy before. Budoy was diagnosed with epilepsy in his 7 day old and he was a yellow baby when he was born.

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Medication History Budoy has an allergies or adverse effects on the different kinds of antibacterial drugs. He had started taking Phenobarbital that is mixed with water at the age of 7 days old when the patient was diagnosed with simple partial seizure. At the age of 10 years old 10/12/05 he was admitted to a hospital and on that time he was already diagnosed with status epilecticus. His first dose medication in the hospital was at 11:40AM on 10/12/05. Phenytoin 45 mg was injected to Budoy as a Loading dose then 60mg IV of 12 as maintenance dose to start 8 from the loading dose. At 7:15PM Budoy has a temperature of 38.5 C and for that case he was injected with Paracetamol 250mg IV. On the 10/15/05 Budoy was given a Phenytoin 100mg Oral Dose and Phenobarbital 60mg tab. After 3 days, the Phenytoin was discontinued and Phenobarbital was taken by Budoy as maintenance until at the present. According to his auntie the last time she took a prescription drug was on the last week of December 2011 wherein the last attack of seizure occurs to Budoy. He has not taken any alternative drug. Review of Systems Watery stool, vomiting and abdominal pain. Physical Examination Budoy is well developed. He is 49 kg in weight 56 in height. His vital signs include a blood pressure of 110/80 mm Hg. All the data of physical examination of Budoy is within the normal limits. Laboratory Diagnostic Test Results The result of HGB hemoglobin is 131 g/L, HCT hematocrit 0.39, RBC (Red Blood Cells) 4.66, MCV 77.9, MCH 28.1, MCHC 36.1, WBC (White Blood Cells) 10.80 with 0.31% neutropilia, 0.07% lymphocytes and 0.02% monocytes. The platelet count is 248 and none has found in fecalycis.

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Patient Problem List  Problem #1 Sedation is the major side effect of Phenobarbital.  Problem #2 Long-term use of Phenobarbital can diminution the intelligence of the patient, impairment of learning the memory, impaired school performance, behavioral abnormalities, depression, and mental confusion in elderly.  Problem #3 Cooled temperature can cause lethargy to the patient.  Problem#4 Coffee addiction. Counsel regarding the interaction of coffee and Phenobarbital.  Problem#5 Special child. Progress There is a progress on Budoys Loss in Bowel Movement and stop in vomiting. The blood pressure and temperature is in the normal state. Other Information For the plans of additional diagnostic procedures and therapeutic interventions, and plans of follow up after hospitalization, Budoy will still continue the maintenance medication of Phenobarbital but for some cases that will occur, paracetamol/acetaminophen must not be taken with Phenobarbital because barbiturates may increase the hepatotoxic potential of acetaminophen and decrease therapeutic effects. Budoy must also lessen his drinking of coffee.

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