7What is a Seizure?A seizure begins when one or more cells send electrical messages that cause an inappropriate burst of electrical activity.This can cause surrounding neurons to generate their own electrical discharges which can spread throughout the entire brain.
8What is a Seizure?Abnormal discharge of brain cells resulting in a change of behavior, movement, sensation or awareness.During a seizure a person may feel, move, think or act differently. This is because a seizure can temporarily disturb many of the brains normal functions.
12What is Epilepsy?Epilepsy is the term applied to the state of recurrent seizures.A condition of the brain, of various causes, which predisposes the patient to recurrent epileptic seizures.Epilepsy is a tremendously variable condition in terms of its cause, seizure types and response to treatment.
13EpilepsyOur understanding of epilepsy has increased dramatically over the last 20 years.Accurate seizure characterization has aided in determining prognosis and selection of medicationSeveral new anti-epileptic medications provide excellent seizure control with less side effects than older medications.Advances in surgery and vagal nerve stimulation.
14Epilepsy StatisticsEpilepsy is one of the most common neurologic diseases.Affects approximately 1% of the population (2 million people in the USA).Approximately 10% of the population will have a seizure at some point in their lifetime.
17Antiepileptic Medications Decreases the frequency or severity of seizures in people with epilepsy.Treats the symptom of the epilepsy (the seizure) and not the underlying condition (the epilepsy).Goal is to improve quality of life by reducing the frequency of seizures with minimal side effects.
18History of Antiepileptic Medications 1912 Phenobarbital was the primary medication used for seizures.Used for generalized tonic-clonic and to a lesser extent partial seizures. No effect on absence seizures.Sedative effect occurred in many people. Hyperactivity noted in children.
19History of Antiepileptic Medications 1938 Diphenylhydantoin (Dilantin) was discovered to have antiepileptic properties.Similar effectiveness to phenobarbital.Less sedative side effects.
20History of Antiepileptic Medications 1960-1974 U.S. Food and Drug Administration (FDA) imposed new regulations on pharmaceutical companies.Medications were now required not only to be safe but they had to be proven effective against the illness it was designed to treat.Only one medication for seizures was developed during this time. Valium was found to be an effective treatment for status epilepticus.
26Antiepileptic Medications How they work? Mechanisms To Target Excitation (Too much)- Flow of Sodium or Calcium into neuron- Neurotransmitters (Glutamate, Aspertate)Inhibition (Too little)-Flow of Chloride in, or Potassium out of neuron-Neurotransmitter (GABA)
30When to Treat? Are the episodes really seizures? EEG: Normal or abnormal?Frequency and type of episodes?Are there other neurologic problems?What is the cause of the seizures? Can the underlying problem be treated rather then treating the symptom (i.e. the seizure)?
31When Not to Treat Single seizure No history Neurologically normal Young ageSide effect concerns
32First SeizureStudies have shown that a otherwise normal child who had a single seizure has a 15% chance of having a second seizure if left untreated.Physicians will typically wait until a second or third seizure before initiating treatment with antiepileptic medication.
33First SeizureFor a child who is neurologically abnormal or has an abnormal EEG- the risk of subsequent seizures is substantially increased to between 50-60%.
34When to Treat? Risk-Benefit Ratio In determining whether to treat physicians consider many factors.The benefits of further seizure activity is weighed against the potential side effects of the antiepileptic medications.The decision to treat is a highly individualized one.
35Key Concepts in Antiepileptic Treatment -Metabolism- The process by which medications are broken down and eliminated by the body.Most antiepileptic medications are metabolized by the liver.Some antiepileptic medications are metabolized by the kidneys.
36Key Concepts in Antiepileptic Treatment -Metabolism- Children generally have a faster metabolism and thus require higher then expected dosages of medications to maintain adequate blood levels.Older people typically have slower metabolisms and thus require less medication. Often they can become toxic on normal dosages of medication.
37Key Concepts in Antiepileptic Treatment Half-life The time it takes your body to eliminate half the medication in your body.After one half-life the amount of medication in your body will decrease by 50 %.After 5 half-lives 95% of the medication will be removed from your body.Half-lives vary greatly among seizure medications.
38Key Concepts in Antiepileptic Treatment Steady State A balance obtained when the amount of medication you take into your body equals the amount being eliminated.May take days to reach a steady state when starting or changing doses of medications.Full therapeutic effect of a medication is not reached until steady state is achieved.
39Key Concepts in Antiepileptic Treatment Therapeutic Range The blood levels of medication that for most people will provide an adequate seizure reducing effect without excessive side effects.Treat the person not the range! Everyone responds differently. Some people can be effectively treated with blood levels above or below the therapeutic range.
41Key Concepts in Antiepileptic Treatment Mechanism of Action How do medications work? For many medications this is still not well understoodProposed mechanisms involve increasing the amount of inhibitory neurotransmitters or changes in the flow of ions (sodium or chloride) across the neuron cell membrane.
42Factor Influencing Drug Selection Many antiepileptic medications are effective against specific seizure types.It is very important to know the specific type or types of seizures a patient is having so that the appropriate medication can be chosen.On occasion the wrong medication can actually make seizures worse.
43Factor Influencing Drug Selection Seizure typeSyndromeSide effectsPatient ageLifestyleChildbearing potentialOther medications
44Factor Influencing Drug Selection Monotherapy or Polytherapy Monotherapy is usually the preferred treatment.A single drug is prescribed in increasing increments until seizures are controlled or toxicity occurs.If the drug is ineffective or side effects occur, the drug is slowly withdrawn while another medication is slowly introduced.
45Advantages of Monotherapy 70-80% of patients are controlled on monotherapy.Fewer side effects.No drug interactions.Easier dosing = Greater complianceLower cost.
47Advantages of Polytherapy May control an additional 30% of patients that could not be controlled with monotherapy.May provide synergistic effects. (1+1=3)
48Side Effects All seizure medications can have side effects. Side effects can be grouped as:Dose relatedDose unrelated (occur at any dosage)Idiosyncratic
49Side Effects Dose related Some effects are dose related. That is they become more likely as the amount of medication is increased.Sleepiness, slurred speech, and unsteadiness are common effects of seizure medications at higher doses.
50Side Effects Dose unrelated (Common at any dose) Some side effects can occur at any dosage.Examples include double vision, weight gain, hyperactivity, sleep disturbances, irritability, hair growth, gum growth, and changes in mood.On occasion these effects are seen at the start of treatment and gradually get better with time.
51Side Effects Idiosyncratic A rare side effect that occurs because of a patients individual sensitivity or allergic reaction to a particular medication.Examples include: Liver failure, aplastic anemia, severe rashs (Steven Johnson Syndrome).
53Side Effects Pregnancy All seizures medication pose some risk to the developing fetus.None of the commonly used seizure medication are absolutely contraindicated in pregnancy.Possible side effects include cleft palate/lips, cardiac abnormalities, and spinal tube defects.
54Side Effects Pregnancy Antiepileptic medications can reduce the effectiveness of certain birth control pills.It is important to tell your doctors about all the medications you are taking so that potential interactions can be discussed and avoided.
55Side Effects Pregnancy Folic acid is frequently prescribed to all women of child baring age as it is believed to protect against some birth defects.Good news! 90% of women with epilepsy who become pregnant will give birth to normal healthy babies.
57ComplianceThe degree to which the patient follows the physicians directions on how and when medications should be taken.73% of people with epilepsy were found to be compliant with medications.Compliance is very important in epilepsy treatment as blood levels of medications will fall low if dosages are missed.
58Reasons for non-compliance Do not need so much medicationUnpleasant side effectsMaking the drug last longer because of costForgetfulnessConfusion about dosages and timesInconvenience of scheduleMisunderstand directions
59Effectiveness of Treatment 75-80% of patients with epilepsy will have reliable long term control of their seizures with currently available medications.For the remainder of patients with intractable seizures other options exist such as epilepsy surgery, neuro-stimulators and the ketogenic diet.
60Discontinuing Antiepileptic Medications Antiepileptic medications may not have to be taken for a lifetime.When seizures have been controlled over a period of time (usually one to two years), there is a good chance that withdrawal of medication will be successful.
61Factors Associated with Seizure Recurrence Abnormal EEGHard to control seizuresNeurologic deficitsEpilepsy type
62Factors Associated with Non-Recurrence in Adults Primary generalized seizure typeUnder 30 years of agePrompt initial control2-5 years of seizure freedom
63Discontinuing Antiepileptic Medications 65-70% of children who are free of seizures on antiepileptic medications will remain seizure free after the drugs are withdrawn.
64Newer Treatments Antiepileptic Medications Research has provided insight into the pathophysiology of epilepsy at the molecular and genetic level enabling medications to be developed that target these mechanismsNot just ‘more of the same’Unique mechanisms of actionImproved pharmacokinetics
65Newer Antiepileptic Medications Similar effectiveness to established AEDs in the treatment of partial seizuresAll AEDs have adverse effectsNot appropriate for all seizure typesPossible teratogenicityLimited data available for efficacy and safetyMost used as adjunctive therapy
67Sabril (Vigabatrin)Approved as monotherapy for patients 1 month to 2 years of age with infantile spasms.Approved as add-on therapy for adults with complex partial seizures.Can cause eye injury (Retinal damage).
68Banzel (Rufinamide)Approved for the treatment of seizures for children and adults (> 4 years old) with Lennox-Gastaut Syndrome (2008).
69Vimpat (Lacosamide)Approved as add-on treatment in adults with partial onset seizures (2008).Unique mechanism of action.Low side effect profile.Rapid effectiveness
70Onfi (Clobazam) Approved in 2011 Adjunctive (add-on) treatment for seizures associated with Lennox-Gastaut syndrome in adults and children 2 years of age and older.Atonic (“drop seizures”), tonic, or myoclonic seizures
71Newer Treatments Medications in Development Carisbamate (Partial seizures)Retigabine (Partial seizures)Eslicarbazepine (Partial seizures)Perampanel (Partial seizures)Brivaracetam (Generalized tonic seizures)FluorofelbamateJZP-4, PID, Valrocemide, Ganaxolone
72New Treatments Devices/Surgical Vagus Nerve StimulatorDeep Brain StimulationNeuropaceEpilepsy Surgery
74Vagus Nerve Stimulator FDA approved in 1997 (Seizures),2005 (Depression)Electrical stimulus applied to the Vagus Nerve and has been found to reduce seizure frequencyTypically reserved for patients with difficult to control epilepsy.Implantation takes 1-2 hours under general anesthesia.
75Vagus Nerve Stimulator Patients/Caregivers can turn the device on by using hand held magnetLow side effects: Cough/ deepening of voice during stimulation.After one year:1/3 have excellent response (90% reduction)1/3 have good response (50% reduction)1/3 little to no response
76Newer Treatments Neuro-stimulators Deep Brain Stimulation Promising new technology for medically-refractory seizures.Stimulator electrodes are placed deep within the brain (thalamus or cerebellum) which are then connected to a pacemaker-like device in the chest.
80Newer Treatments Epilepsy Surgery Certain patients in whom medication has failed to provide seizure control are evaluated for epilepsy surgerySurgery is restricted to those patients whose seizures originate from an identifiable focus in the brain.
84Newer Developments MEG (Magnetoencephalography) Measures the small electrical currents arising inside the neurons of the brain.Similar to EEG but provides greater accuracy.Used to locate where seizures are coming from within the brain.Can be used to map brain functions
85Alternative Treatments Ketogenic Diet Developed in the 1920’sHigh fat, low carbohydrate, adequate protein diet (4:1 ratio)Forces body to burn fats producing ketonesEffective in half the patients who try it
86Alternative Treatments Ketogenic Diet Not easy. Requires careful weighing and calculating of food caloriesComplications: Growth delay, bone fractures, kidney stones and elevated cholesterol levels
87Alternative Treatments Biofeedback Method of using relaxation or imagery to change body functions such as breathing, heart rate, and blood pressureThese functions are monitoredA stressful situation is presented and relaxation techniques are utilizedPatient is able to view these functions and the see the differences between stressed and relaxed states
88Alternative Treatments Biofeedback Has been shown to help people with high blood pressure, headaches, and pain.Patients who have seizures triggered by anxiety or stressful situations may benefit
90Alternative Treatments Melatonin Natural hormone produced by the pineal gland in the brainFrequently used as a sleep aidStudy results with respect to helping seizures have been inconclusive.
91Alternative Treatments Vitamins Necessary for good health, however……Large doses of vitamins have not been shown to be of any benefit in reducing seizure frequencyPatients on seizure medication may require supplements of calcium and Vitamin D for bone health.