Epilepsy: Treatment & Recommendations PDF

EPILEPSY: Treatment & Recommendations 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 Epilepsy Definition: Epilep...

EPILEPSY: Treatment & Recommendations 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 Epilepsy Definition: Epilepsy is a chronic disorder characterized by recurrent seizures (or convulsions). Seizures are episodes of brain dysfunction resulting from abnormal discharge of cerebral neurons Epidemiology Approximately 50 million people currently live with epilepsy worldwide The estimated proportion of the general population with active epilepsy at a given time is between 4 and 10 per 1000 people Globally, an estimated 2.4 million people are diagnosed with epilepsy each year Classification of seizures I. Partial (focal) Seizures A. Simple Partial Seizures B. Complex Partial Seizures C. Partial seizures secondarily generalized II. Generalized Seizures D. Generalized Tonic-Clonic Seizures E. Absence Seizures F. Tonic Seizures G. Atonic Seizures H. Clonic Seizures I. Myoclonic Seizures J. Infantile Spasms Evaluation of the first seizure in adults 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 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 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. 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 Diagnostic Studies Lab studies – CBC, serum glucose, Calcium, Magnesium, renal function studies, drug and toxicology screens Lumbar puncture – if an infectious process is suspected 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) Hospitalization First seizure with a prolonged post-ictal state or unusual features Status Epilepticus An associated systemic illness History of significant head trauma 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) 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 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 High Risk Patients A history of serious brain injury Lesion on CT or MRI that could promote recurrent seizures Focal neurologic exam Mental retardation Partial seizure as the first seizure An abnormal EEG Absence, myoclonic, and atonic seizures are more likely to recur Treatment approach  Treatment is typically reserved for people who have had at least two seizures  There could be circumstances in which treatment after a first seizure is appropriate (e.g. presence of a structural lesion on neuroimaging)  Most people with epilepsy eventually become free of seizures on antiepileptic drugs About 20-30% of patients continue to have seizures despite treatment  Epilepsy carries an increased risk of morbidity and premature mortality 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 Pharmacological treatment Based on seizure type/ epilepsy syndrome Refer to NICE guideline 2012, Consensus Guideline on the Management of Epilepsy 2010 (Malaysia) First Generation AED Phenytoin Phenobarbital Clonazepam Carbamazepine Sodium Valproate Ethosuximide Primidone Second Generation AEDs Topiramate (Topomax – 1996) Oxcarbazepine (Trileptal – 2000) Lamotrigine (Lamictal – 1994) Gabapentin (Neurotin – 1993) Levetiracetam (Keppra – 1999) Tiagabine (Gabitril – 1997) Zonisamide (Zonegran – 2000) Pregabalin (Lyrica - 2005) Felbamate (Felbatol-1993) Vigabatrin (Sabril 2005-2006) Second Generation AEDs  Generally lower side effect rates  Little or no need for serum monitoring  Once or twice daily dosing  Fewer drug interactions  There is no significant difference in efficacy with the second generation agents  Higher cost associated with the new agents  Monotherapy is well established for Lamotrigine and Oxcarbazepine  The other agents are undergoing trials and many have completed monotherapy trials AEDs In General  In all people with epilepsy, the goal should be to achieve seizure freedom  The patient needs to know that AED treatment is a commitment and non-compliance can be dangerous  The choice of initial monotherapy – several important studies (including SANAD) and advice from the National Institute for Health and Clinical Excellence (NICE)  The AED strategy should be tailored to each patient’s seizure type, epilepsy syndrome, co- treatment, comorbidity, lifestyle issues, and preferences AEDs In General The duration of each treatment trial before deciding on continuing or changing to an alternative drug depends on the occurrence of side effects and seizure frequency AED Special Considerations OCPs Expected contraception failure rate 0.7 per 100 women years using OCPs. Women taking enzyme inducing AEDs it is 3.1 per 100. AED Special Considerations OCPs This occurs with all the first generation agents with the exception of valproate. Felbamate,topiramate, oxcarbazepine induce enzyme activity and therefore decrease efficacy of OCPs Women on AED’S that induce enzymes should be on a OCP with at least 50 mcg of the estrogen component AEDs in General Enzyme inducing Drugs Phenytoin Carbamazepine Phenobarbital Felbamate Topiramate Oxcarbazepine Pregnancy Considerations Consider withdraw of AEDs if patient is a good candidate Use monotherapy where appropriate Folate 1-4 mg per day in all women on AEDs The risk of fetal malformations are increased in pregnant women on AEDs Seizures during pregnancy can induce miscarriage Seizures during pregnancy can be deleterious to the mother or fetus Status Epilepticus Status epilepticus (SE)  Generalised convulsive and non-convulsive SE neurological and medical emergencies ≥ 5 mins of continuous seizure activity or repetitive seizures with no intervening recovery of consciousness  Simple partial SE does not usually involve alteration of consciousness seizures are often localised to the part of the body in which they originate, and motor activity can last for hours, days, or even longer SE etiology Causes varied Any neurological insult or systemic abnormality capable of inducing a seizure can cause SE The single most common cause of SE is anticonvulsant drug non-adherence or withdrawal  SE classification 1. Generalised convulsive SE  paroxysmal or continuous tonic or clonic motor activity that may be symmetrical or asymmetrical  includes primary and secondary generalised seizures 2. Non-convulsive SE  a wide variety of clinical manifestations, including coma, confusion, disorientation, altered affect, bizarre behaviour, delusions, hallucinations, and paranoia  further sub-divided into 2 major categories:  Absence SE  Complex partial SE 3. Simple partial SE  seizures that are localised to the part of the body in which they originate  focal clonic activity; however, sometimes they will only have subjective changes or an isolated aphasia.  consciousness preserved Goal of therapy for SE Rapid termination of the seizure activity to reduce neurological injuries and deaths Generalised convulsive SE treatment in community  General protective measures - eg, ensuring the head is protected, releasing any constricting neck wear, moving away from a dangerous position.  Secure the airway and assess respiratory and cardiac function.  Buccal midazolam  first-line treatment for prolonged or repeated seizures.  Administer rectal diazepam if preferred or if buccal midazolam is not available.  IV lorazepam  if IV access is established and resuscitation facilities are available. Generalised convulsive SE treatment in hospital  Secure airway, give high-concentration oxygen.  Assess cardiac and respiratory function, check blood glucose levels and secure IV access in a large vein.  1st line  IV lorazepam  IV diazepam if IV lorazepam is unavailable, or buccal midazolam if unable to secure immediate IV access  Administer a maximum of two doses of the first-line treatment (including pre-hospital treatment)  If seizures continue, administer IV phenobarbital or phenytoin as second-line treatment.  Fosphenytoin (a prodrug of phenytoin) can be given more rapidly and, when given as IV, causes fewer injection-site reactions than phenytoin Generalised convulsive SE treatment in hospital Other therapy Correct hypoglycaemia if present. Parenteral thiamine – if alcohol abuse is suspected. Pyridoxine (vitamin B6) – if the SE is caused by pyridoxine deficiency Emergency investigations in hospital Pulse oximetry; blood gases. Blood for glucose, renal function, electrolytes, liver function, calcium and magnesium; FBC and clotting; AED levels. Generalised convulsive SE treatment in hospital – Further management  Identify and treat any underlying cause. Status is associated with community-acquired bacterial meningitis and seizures.  Identify and treat medical complications – eg. CXR to evaluate the possibility of aspiration.  Regular AEDs should be continued at optimal doses and the reasons for SE should be investigated.  Only prescribe buccal midazolam or rectal diazepam for use in the community if there has been a previous episode of prolonged or serial convulsive seizures. Thank you