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EPILEPSY Review of new treatments and Recommendations
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OBJECTIVES To understand the work-up of new onset seizures. Understand the differential diagnosis of Paroxysmal events Be familiar with the new medications used to treat epilepsy and special considerations in there use.
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Glossary Seizure - An alteration in behavior sensation or awareness caused by an abnormal neuronal discharge of the brain Epilepsy – The recurring tendency to have seizures having excluded an underlying reversible etiology
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Epidemiology Prevalence.5-1.0% of the population Each year 300,000 people seek medical care for new onset seizures. 50% are subsequently diagnosed with epilepsy More than 2 million Americans have active epilepsy of which 17% are under the age of 18
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Differential Diagnosis of Paroxysmal Events Paroxysmal symptoms may be either epileptic or nonepileptic (physiological or psychogenic) The interview and exam is aimed at narrowing the possibilities Seizures in many individuals are provoked, this is not epilepsy
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Differential Diagnosis of Paroxysmal Events ( Nonepileptic) Syncope Migraine Movement disorders TIA Sleep disorders TGA Various psychogenic causes
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Evaluation of the first seizure in adults
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History Was the event a seizure? Are there witnesses What were the circumstances under which the event occurred Is there an obvious provoking cause Tongue biting, incontinence, post – ictal state, muscle soreness
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History Medication history Past Medical history – Risk factors for epileptic seizures include a history of head injury, stroke, alcohol and drug abuse Family history – Absence and myoclonic seizures may be inherited.
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Physical and Neurologic Examination The purpose of the neurologic exam initially is to look for focal features Screen acutely for musculoskeletal trauma (fractures etc.) Remember the possibility of aspiration Pneumonia etc.
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Diagnostic Studies Neuroimaging – Brain MRI is the preferred modality. CT brain is done in the emergency setting to rule out acute pathology but should be followed up by MRI if no contraindication PET and SPECT imaging and functional imaging are not used in the initial evaluation.
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Diagnostic Studies Lab studies – CBC, serum glucose, Calcium, Magnesium, renal function studies and drug and toxicology screens. Lumbar puncture – done if an infectious process is suspected. This may be misleading if the seizure was prolonged.
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Diagnostic Studies EEG This study is helpful if positive A normal EEG does not rule out epilepsy The study is more sensitive if the patient sleeps during the record (sleep deprived)
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Hospitalization First seizure with a prolonged post-ictal state or unusual features Status Epilepticus An associated systemic illness History of significant head trauma
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Initial Work-Up Primary Objectives Did the event result from a correctable systemic process Is the patient at risk for future episodes
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Single Unprovoked Seizures Common affecting 4% of the population by age 80 30%-40% of patients with a first seizure will have a second unprovoked seizure ( epilepsy)
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Single Unprovoked Seizures Risk factors for seizure recurrence include a history of neurologic insult, focal lesions on MRI, epileptiform EEG, and family history of epilepsy Adult patients with these risk factors have a 60%-70% of recurrence
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Antiepileptic Drug Therapy AED therapy is not necessary if a first seizure provoked by factors that resolve AED therapy may be indicated if there is a permeate injury to the brain (stroke,tumor) In general AED therapy is started if there is a high risk of recurrent seizures
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High Risk Patients A history of serious brain injury Lesion on CT or MRI that could promote recurrent seizures Focal neurologic exam Mental retardation
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High Risk Patients Partial seizure as the first seizure An abnormal EEG Absence, myoclonic, and atonic seizures are more likely to recur
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Choosing an AED Treatment should start with one drug titrated to the appropriate levels Monitor response and side effects Combination therapy should be attempted only if two adequate monotherapy trials have occurred
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Second Generation AED’S Topiramate (Topomax – 1996) Oxcarbazepine (Trileptal – 2000) Lamotrigine (Lamictal – 1994) Gabapentin (Neurotin – 1993) Levetiracetam (Keppra – 1999)
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Second Generation AED’S Tiagabine (Gabitril – 1997) Zonisamide (Zonegran – 2000) Pregabalin (Lyrica - 2005) Felbamate (Felbatol-1993) Vigabatrin (Sabril 2005-2006 Available in Canada and Europe)
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Second Generation AED’S With the exception of Felbamate second generation AED’S have advantages over first generation agents.
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Second Generation AED’S Generally lower side effect rates Little or no need for serum monitoring Once or twice daily dosing Fewer drug interactions
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Second Generation AED’S There is no significant difference in efficacy with the second generation agents Higher cost associated with the new agents
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Second Generation AED’S Monotherapy is well established for Lamotrigine and Oxcarbazepine The other agents are undergoing and many have completed monotherapy trials.
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AED’S In General The most important factor in determining success of drug therapy is the duration of the epilepsy The patient needs to know that AED treatment is a commitment and non- compliance can be dangerous
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AED Special Considerations BCP’s Expected contraception failure rate.7 per 100 women years using BCP’S. Women taking enzyme inducing AED’S it is 3.1 per 100.
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AED Special Considerations BCP’s This occurs with all the first generation agents with the exception of valproate. Felbamate,Topiramate, Oxcarbazepine induce enzyme activity and therefore decrease efficacy of BCP’S Women on AED’S that induce enzymes should be on a BCP with at least 50 mcg of the estrogen component
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AED’S in General Enzyme inducing Drugs Phenytoin Carbamazepine Phenobarbital Felbamate Topiramate Oxcarbazepine
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Pregnancy Considerations Consider withdraw of AED’S if patient is a good candidate Use monotherapy where appropriate Folate 1-4 mg per day in all women on AED’S
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Pregnancy Considerations The risk of fetal malformations are increased in pregnant women on AED’S Seizures during pregnancy can induce miscarriage Seizures during pregnancy can be deleterious to the mother or fetus
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Pregnancy Considerations The possibility of prenatal diagnosis of malformations can be considered with AFP levels and ultrasonography
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Cost Felbamate 600mg #180 - $376.00 Neurotin 400mg #90 – $132.00/74.00 Lamictal 150mg #60 –$208.00 Topamax 200mg #60 – $223.00 Gabitril 32mg #60 – $152.00
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Cost Keppra 750mg #60 -$190.00 Trileptal 600mg #60 - $211.00 Zonisamide 100mg #90 - $184.00 Lyrica 300mg #90 – 180.00
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AED’S in General Calcium and vitamin D supplements should be used in patients on enzyme inducing drugs Generics should not be used if at all possible unless it is the same generic or the patient has a very easy to control seizure problem
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Conclusions The work up of a first seizure is straightforward in most instances but relies on a good History and consideration of the differential diagnosis. New medications approved for epilepsy are effective and have a lower side effect profile.
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Conclusions Use folic acid, calcium and Vitamin D supplementation in patients on the first generation AED’S and probably the second generation ones as well.
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