Epilepsy Final

EPILEPSY Presented By Amol.B.Lavate (M.Pharm)1st year Pharmacy Practice, KLES University Belgaum.

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CONTENT  INTRODUCTION  FACTS  CAUSES OF SEIZURES  POSSIBLE SEIZURE TRIGGERS

 PATHOPHYSIOLOGY  TYPES OF EPILEPSY  CLASSIFICATION OF SEIZURES  PREVALENCE  SYMPTOMS OF EPILEPSY  SCREENING & DIAGNOSIS  TREATMENT  ACTIONS OF ANTISEIZURE DRUGS  USE OF ANTISEIZURE DRUGS

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INTRODUCTION 

Epilepsy: Periodic and unpredictable seizures caused by the rhythmic firing of large groups of neurons may range from mild twitching to loss of consciousness and uncontrollable convulsion

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• Seizures-:A seizure is a paroxysmal behavioral spell generally caused by an excessive disorderly discharge of cortical or sub cortical nerve cells  

Seizures usually occurs without warning and without the person's awareness of what is happening. Some people with epilepsy will have only an occasional seizure, while others will have many on a daily basis. 3

Facts about Epilepsy   

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Epilepsy affects 2.7 million Americans, more Americans than cerebral palsy, multiple sclerosis and Parkinson’s Disease combined. Approximately 200,000 new cases of epilepsy occur each year. Everyone's brain has the ability to produce a seizure under the right conditions. Epilepsy can develop at any age. However, it is diagnosed most often before the age of 20 and after the age of 60. With the appropriate treatment, up to 70% of people with epilepsy could be seizure free. Only a few percent of people with epilepsy are affected by flashing lights– this is called photosensitivity. The Greek philosopher Hippocrates (460-377 BC) was the first person to recognize that epilepsy starts in the brain. Ten percent of the American population will experience a seizure at least once in their lifetime. 1 person in 20 will have a seizure at some time in their life

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Causes of seizures •Heredity - th e risk o f g e ttin g e p ile p sy is 2.5 times greater with a family history of seizures than when no family member has had the disorder •Head trauma - the more severe the injury, the greater the risk of developing epilepsy •Brain tumor and stroke •Poisoning - such as lead poisoning. More than 5,000 people annually suffer seizures caused by alcoholism. •Infections - such as meningitis, viral encephalitis, mumps, measles and diphtheria •Maternal injury - such as infection or systemic illness affecting the fetus' developing brain during pregnancy

Vascular, 10%

Congenital, 8%

Trauma, 6% Tumor, 4% Degenerative, 4% Unknown, 65%

Infection, 3%

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Possible seizure triggers

S tre ss

Alcohol

U n h e a lth y n u tritio n

Skipping meals

Lack of sleep, exhaustion Irregular medication Flickering lightsIllness and allergies

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PATHOPHYSIOLOGY (I)

•Normal brain function involves "communication" between millions of nerve cells (neurons) •A nerve cell is made up of a cell body and branches called axons and dendrites which join other neurons at junctions called synapses •At any one time, there are nerve cells which are resting, exciting or inhibiting other nerve cells •Electrical signals are sent from the cell body along the axon to the synapse, these electrical signals being the result of ion (Na+, K+ , Ca2+) currents across channels in the nerve cell membrane •Chemical signals (neurotransmitters) pass across synapses between neurons

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PATHOPHYSIOLOGY (II) •Neurotransmitters cross the synaptic gap between neurons and fix to receptor points of the adjoining neuron •Some neurotransmitters function to excite the joining neuron (eg. glutamate) to send a further electrical signal. Other neurotransmitters function to inhibit the joining neuron (eg. GABA) and inhibit electrical signals passing down that neuron •It is by these electrical and chemical pathways that the millions of neurons within the brain communicate and function normally •seizures occur when there is an imbalance within these excitatory and inhibitory circuits in the brain, either throughout the brain (generalized epilepsy) or in a localized part of the brain (focal epilepsy), such that neurons fire off in an abnormal fashion •Mechanism of AEDs to prevent –Altering electrical transmission along neurons by affecting ion (Na+, K+ , Ca2+) channels in the cell membrane. –Altering chemical transmission between neurons by affecting neurotransmitters (GABA,glutamate) in the synapse

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CLASSIFICATION OF SEIZURES Seizure Classification Partial

Generalized

seizure activity starts in one area of the brain

seizure involves whole brain & consciousness is affected

Simple

Complex

Retains awareness

Altered awareness and behavior

Secondary generalization

( spreading from one area to the whole brain )

Tonic Clonic

Absence

“grand - mal ” or

“petit mal ” or starting fit or trance like state

convulsion Loss of consciousness , stiffening of body then jerking of limbs

Tonic or Atonic

‘ drop attack ” Abrupt fall , either with stiffening ( tonic ) or with loss of muscle tone ( atonic or “ astatic ” attacks )

Myoclonic Sudden muscle jerks

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SEIZURE CLASSIFICATIONS:

Generalized

Jacksonian

Focal

PARTIAL SEIZURES Simple partial seizures. • These seizures don't result in loss of consciousness. They may alter emotions or change the way things look, smell, feel, taste or sound. •

Complex partial seizures. • These seizures alter consciousness, causing you to lose awareness for a period of time. Complex partial seizures often result in staring and non purposeful movements — such as hand rubbing, lip smacking, arm positioning, vocalization or swallowing. 11

Generalized Seizures  Absence seizures (petit mal) • These seizures are characterized by staring, subtle body movement and brief lapses of awareness. •

 Myoclonic seizures • These seizures usually appear as sudden jerks of your arms and legs. •

 Atonic seizures • Also known as drop attacks, these seizures cause you to suddenly collapse or fall down. •

 Tonic- clonic seizures (grand mal) • The most intense of all types of seizures, usual sequence is aura-cryunconsciousness -tonic spasm of all body muscles –clonic jerk followed by prolong sleep & depression of all CNS functions. • 12

Prevalence of seizure types Generalized tonic clonic, 23%

Simple Partial, 14%

Other generalized, 8%

Partial unknown, 7%

Complex Partial, 36%

Absence, 6% Myoclonic, 3% Unclassified, 3%

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Symptoms of Epilepsy

lsion with or Blackout withoutoraSudden confused fever fear memory , anger for Blank no reason jerks of arms, legs o staring SuddenMuscle stiffening

Conditions that may be mistaken for epilepsy •Seizures associated with high fever •Fainting •Sleep disorders: nightmares, narcolepsy, cataplexy •Psychiatric disorders: panic attacks, fugue states, psychogenic seizures •Migraine headaches •Childhood breath-holding episodes

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Screening & Diagnosis Electroencephalogram (EEG)

 Computerized tomography (CT)

 Magnetic resonance imaging (MRI)

 Positron emission tomography (PET) •

Single-photon emission computerized tomography 15

electroencephalography The EEG or electroencephalography, developed by Professor Hans Berger in the 1920’s is one of the most determinant and specific diagnostic tests due to the fact that it records the electrical activity of the brain in a safe and painless graphical manner. Each trace of its recording corresponds to a different region of the brain and they could be easily interpreted by the specialists.

Computerized tomography (CT) The CT scan, which stands for computed tomography, is equivalent to an X-Ray of the head which would usually appear normal in most patients with Epilepsy. Decreases in brain substance, scar tissue, tumors, abnormal blood vessels or abnormal spinal fluid circulation are a few of the abnormalities that might be projected with this kind of test.

MAGNETIC RESONANCE IMAGING(MRI) Magnetic Resonance Imaging [MRI] was first introduced in the USA in the early 1980s revolutionizing the practice of neurology and neurosurgery because of the excellent detail resemblance of the brain’s structure. This is extremely helpful because it identifies brain scar tissue, areas of abnormal brain development or dysplasia, small brain tumors, blood vessel abnormalities, and changes in the brain’s white matter.

Positron emission tomography PET scans use injected radioactive material to help visualize active areas of the brain. The radioactive material is tagged in a way that makes it attracted to glucose. Because the brain uses glucose for energy, the parts that are working harder will be brighter on a PET image. •• After the radioactive material is injected, it will take between 30 and 90 minutes for the substance to accumulate in your brain tissue. During this waiting period, you will be asked to rest quietly and not talk or move around much. The actual scan takes 30 to 45 minutes. The amount of radioactive material used in the test is very small, and its glucose binding activity in the brain lasts only a short period of time. 

Single-photon emission computerized tomography(SPECT) • This type of test is used primarily in people being evaluated for epilepsy surgery when the area of seizure onset is unclear on MRIs or EEGs. SPECT imaging requires two scans — one during a seizure and one 24 hours later. Radioactive material is injected for both scans and then the two results are compared. The area of the brain with the greatest activity during the seizure can be superimposed onto the person's MRI, to show surgeons exactly what portion of the brain should be removed

Treatment Algorithm

Treatment Options 

There are four main categories of epilepsy treatments 

Ø Medications 

Ø Ø Surgery 

Ø Ø Ketogenic Diet

Ø Ø Vagus Nerve Stimulation

Ø Ø Other treatments for epilepsy

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Medications 

Each medication has benefits and side effects and different medications are appropriate for different types of epilepsy.

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No one medication is proven to be the best treatment for epilepsy. Only a complete evaluation can determine which medication will work best for each patient.

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Approximately

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50% of seizures are eliminated by medication

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30% of seizures are reduced in intensity and frequency by medication 23

Seizure type and Drug selection Seizure type

First line drugs

Partial ,simple, complex, •Lacosimide with or without secondary •Leveiiracetam •Carbamazepine generalization •Sodium valproate

Generalized absence

Sodium valproate Ethosuximide

Generalized tonic-clonic

Levetiracetam Sodium valproate

Myoclonic

Leveitiracetam Sodium valproate

Second line drugs Clobazam Clonazepam •Gabapentin •Lamotrigine •Phenytoin •Tiagabine •Topiramate •Vigabatrin •Pregabalin •Zonisamide • •

Clobazam Clonazepam •Lamotrigine •Carbamazepine •Clobazam •Gabapentin •Lamotrigine •Phenytoin •Topiramate •Vigabatrin • •

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Phenobarbital

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Actions of antiseizure drugs Antiseizure Drugs act by distinct mechanisms: •increasing effect of GABA , inhibitory neurotransmitter •delaying the influx of sodium and calcium ions into neurons •Major Chemical categories of antiseizure meds: •1. Barbiturates •2. Benzodiazepines •

Barbiturates  phenobarbital ( Luminal ) 60 - 180mg / day  primidone750 - 1000mg / day MOA : potentiate the effects of GABA Indication :  tonic- clonic seizures ,status epilepticus  adjuncts to anesthesia SE :  drowsiness  dizziness  hypotension  respiratory depression  drug tolerance  physical drug dependency & withdrawal syndrome

Benzodiazepines  diazepam ( Valium ) 4 - 40mg / day  clonazepam (Klonopin)1-12mg/day  lorazepam (Ativan)2-6mg/day  clorazepate (Tranxene)7.5-22.5mg/day MOA : intensify GABA action Indication :  short -term severe convulsions, status epilepticus  relieve tension , anxiety & skeletal muscle spasms SE :  ataxia  cardiac depression  drug tolerance  physical drug dependency with withdrawal syndrome

Hydantoin  phenytoin ( Dilantin ) 300 - 400mg / day MOA : delay influx of sodium ions into neurons Indication :  all types of seizure except for absence seizures Side Effects :  gingival hyperplasia  slurred speech  confusion , headache & depression  blood dyscrasias  severe liver toxicity  alopecia  hirsutism  Stevens –Johnson syndrome

Succinimides Ethosuximide (Zarontin)750-1250mg/day MOA : delay calcium influx into neurons Indication : DOC for absence seizures SE ;  anorexia & vomiting  blood dyscrasia  Stevens- johnson syndrome 

Other antiseizure drugs          

Valproates750-2000mg/day  valporic acid ( Depakene)  divalproex Na (Depakote) Indication:  absence seizures  mania  migraine headache SE:  GI upset  Hepatotoxic

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Iminostilbenes  carbamazepine (Tegretol)600-1800mg/day  gabapentin (Neurontin)9002400mg/day  lamotrigine150-500mg/day  topiramate200-400mg/day Indication:  seizure DO that have not responded to other convulsants  trigeminal neuralgia  DOC for partial seizures SE;  Blood dyscrasia  CNS depression  GI upset  Stevens- johnson syndrome

OPERATIVE

STATISTICS SHOW THAT… 70% of patients manage their epileptic attacks with the use of drugs

But the other 30% are treated with surgery.

LOBE st common procedure among adults and adolescents, is the removal of the lobe where the o RESECTION

LESIONECTOM Y

in lesions, such as areas of injury, tumors, or malformed blood vessels.

In a FUNCTIONAL HEMISPHERECTOMY, one hemisphere is disconnected from the rest of the brain, but only a specific area of brain tissue is removed. This surgery is typically done on children younger than 13 years old who have one hemisphere that is not functioning normally.

FUNCTIONAL HEMISPHERECTOMY

MULTIPLE SUBPIAL TRANSECTION

MULTIPLE SUBPIAL TRANSECTION (MST) is used to help control seizures that begin in areas of the brain that cannot be safely removed. The surgeon makes a series of shallow cuts or transections in the brain tissue to interrupt the course of seizure impulses but do not disturb normal brain activity, leaving the person's abilities intact.

Ketogenic Diet 

The ketogenic diet is primarily used in childhood epilepsy.

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The mechanism of ketogenic diet is unknown. The high-fat, low-protein, no-carbohydrate diet mimics some effects of starvation that seem to inhibit seizures.

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The diet is very rigid and carefully controlled and must be supervised by a physician -- sometimes in a hospital setting.

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Ketogenic diets have been used for children with epilepsy for many years with a success rate of approximately 50 percent.

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Vagus Nerve Stimulation (VNS) •Vagus nerve stimulation (VNS) is approved to treat partial seizures in patients 12 years of age or older •Approximately 30 to 50 percent of patients can be expected to have less seizure activity with VNS •The vagus nerve stimulator is surgically implanted under the skin in the chest. The device is attached to a wire that is tunneled under the skin and attached to the vagus nerve, which is located in the left side of the neck •The vagus nerve stimulator is adjusted to automatically stimulate the vagus nerve from every few seconds to every few minutes. •The device does not detect seizure activity. It can be adjusted easily in a physician's office using a laptop computer

OTHER TREATMENTS FOR EPILEPSY     

NATUROPATHY YOGA THERAPY ACUPUNCTURE HYPNOTISM COLLOIDAL SILVER

Naturopathy 

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NATUROPATHY is the belief that avoiding certain drugs such as caffeine and alcohol; chemicals; and maintaining a well-balanced diet high in vitamins D and B6, as well as zinc, calcium, and magnesium, which have anticonvulsant properties, and the amino acid taurine, would help control seizures.

Yoga therapy Yoga therapy aims at developing control over the neuron excitations that triggers the seizure by training the individual to develop an internal balance through techniques of decreasing activity rates at all levels, reaching a deep resting state that heals the mind and body complex.

Acupuncture Acupuncture, China's medical heritage for over 3,000 years, which was introduced into the USA and Canada in the 1970's and that people find helpful when trying to control seizures but that in rare cases may also cause them, seeks to help the body to heal itself but not as a self-help treatment. This therapeutic mode relieves some of the problems which provoke Epilepsy such as stress and poor sleep by restoring the harmony within the individual’s body by concentrating on the patterns of energy that flow through the body just below the surface of the skin. Steel needles are inserted in vital specific areas of the body of the epileptic person that influence the brain energy and flow of blood to the head. Acupuncture treatments usually last from 1 - 18 months, and 65 people showed marked improvements with an absence of seizures during a one year period without the use of standardized drugs. 

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Hypnotism Hypnotism has been proven to be a mean of relief that is normally safe and beneficial for patients with partial seizures. Commonly, to be in a hypnotic state it takes an effort of intense concentration and some studies found a degree of high arousal in the EEGs of people being hypnotized, which means that this could, in certain cases induce a seizure.

Colloidal Silver Colloidal Silver, composed mainly of silver proteins suspended in a liquid, most likely water that are used to treat disorders such as Epilepsy, gonorrhea, and colds. This type of therapy was uncommon until the mid-20th century but is now promoted as a cure for AIDS, cancer, and diabetes. No human clinical data has been found to support its oral use even if it is composed of an essential mineral, and apparently it does not serve any physiological function in the body. Its long term use can cause silver deposition in the skin and mucous membranes leading to an irreversible condition called argyria; therefore pregnant women should abstain from the use of it.

Prognosis 

Certain types of childhood epilepsy resolve or improve with age.

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A seizure-free period of 4 years may indicate that reduction or elimination of medications is possible.

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Death or permanent brain damage from seizures is rare, but can occur if the seizure is prolonged.

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Death or brain damage are most often caused by prolonged lack of breathing and resultant death of brain tissue from lack of oxygen.

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Infrequent seizures may not severely restrict the person's 44 lifestyle.

References

1. Joseph T.Dipiro,Barbera G.Wells,Terry L Schwinghamar,CindyW.Hamlilton-Pharmacotherapy handbook,5th edition2003; 505-22 2. Roger Walkar,Clive Edwards-Clinical pharmacay and Therapeutics 3rd edition 2003;465-81 3. Eric T. Herfindal,Dick R. Gourley-Textbook of Therapeutics drug and disease management,7th edition 2002;1107-11 4. www.unisanet.unisa.edu.au/12163/undlecs2002 5. www.sfn.org/.../epilepsy_illus_large.gif 6. thebrain.mcgill.ca 7. www.aesnet.org/go/professionaldevelopement/educational-opportu 8. www.wellsphere.com/wellpage/epilepsy 9. www.med.uc.edu/neurology/epilepsyinfo.htm

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Thank You

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