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Epilepsy (What Do I Do Now?)
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Section 1: Diagnostic Questions 1. Febrile seizures and first seizures in infants, Daniel Friedman Febrile seizures are common and are often benign with little risk of subsequent epilepsy. However, febrile seizures with complex features may increase the risk of epilepsy later in life or may be the heralding seizure of a severe infantile epilepsy syndrome. 2. Idiopathic Partial Epilepsies (IPE) of childhood, Derek J. Chong Benign rolandic epilepsy, or BECTS, and the benign occipital epilepsies have specific clinical features and electrographic findings that set them apart from other types of epilepsy. The diagnosis of these conditions is important as they impart a high chance of spontaneous and complete remission. 3. Nonconvulsive status epilepticus in hospitalized patients, Daniel Friedman Seizures without overt convulsive activity are common in critically ill and acute brain injury patients. Often the only manifestation is altered mental status and EEG monitoring is required for the diagnosis. Treatment is aimed at controlling seizures to limit secondary neuronal injury while minimizing the adverse effects of therapy. 4. Psychogenic nonepileptic seizures, Carl W. Bazil About 25% of patients with refractory epilepsy who are referred to epilepsy centers actually are found to have psychogenic nonepileptic seizures. These can be very confusing to treating clinicians, as by history they may sound exactly like epileptic seizures. Correct diagnosis usually requires video-EEG monitoring, and diagnosis is critical in redirecting appropriate care for the patient. 5. Frontal lobe seizures, Daniel Friedman Seizures of frontal lobe origin often have little EEG correlate and can have bizarre semiologies that can be mistaken for nonepileptic seizures. Nocturnal onsets and stereotyped features are clues to the diagnosis. 6. Seizure versus parasomnias, Carl W. Bazil Paroxysmal episodes that occur during sleep can be a diagnostic dilemma. History may be imperfect or even nonexistent, as patients may not recall the actual episode, and witnesses may not be present. Careful history may be able to distinguish whether the event is a seizure or a parasomnia, however diagnostic testing with polysomnography and/or video-EEG may be required to confirm the diagnosis. 7. Seizure versus syncope, Carl W. Bazil Sudden loss of awareness could represent syncope or seizure. History is usually helpful in making the diagnosis, as characteristics such as tongue biting, incontinence, and postictal confusion are more suggestive of seizure. Section 2: Treatment Considerations: AEDs 8. First unprovoked seizure, Derek J. Chong Up to 10% of the population will have a seizure in their lifetime, yet only 1% of the population will have recurrent, unprovoked seizures. The first recognized seizure is a frightening occurrence for patients. Standard of care includes an EEG and MRI of the head for prognostication of recurrence, and to rule out symptomatic causes. 9. Initial treatment of idiopathic generalized epilepsy (IGE), Derek J. Chong Patients with idiopathic (or primary) generalized epilepsies are presumed to have a low threshold for seizures that may be of genetic origin. These syndromes comprise 20% of all epilepsy. Treatment consists of broad-spectrum agents with some specific medications used for specific seizure types seen in IGE. 10. Initial treatment of localization related epilepsy (LRE), Derek J. Chong There are over a dozen medications available to reduce the risk of partial onset seizures. The current motto of 'no seizures, no side-effects' requires tailoring the choice of medication based on their characteristics and side-effect profile with the patient's own priorities. Mood and weight change are among the issues that are often important to patients. 11. Treatment of status epilepticus, Daniel Friedman Generalized status epilepticus is a neurological emergency associated with significant morbidity and mortality. Prompt diagnosis and treatment, often guided by EEG monitoring, is necessary. 12. Idiosyncratic reactions - Rash, Daniel Friedman Skin eruptions are common reactions to AEDs and can rarely be serious and life threatening with systemic manifestations. The key to treatment is usually discontinuing the offending drug without placing the patient at risk for seizures. 13. Other idiosyncratic reactions and adverse drug effects, Daniel Friedman AEDs can have rare but serious effects that cannot be predicted by their mechanisms of action or metabolic pathways. These reactions can hepatic dysfunction, hematologic abnormalities, pancreatitis and CNS dysfunction. 14. Generic AED substitutions, Carl W. Bazil Patients and insurers often inquire about lower cost generic alternatives. While these may be appropriate for many patients, in epilepsy the additional variability introduced when using a generic equivalent requires more vigilance than in most other conditions. 15. Withdrawal of AEDs, Carl W. Bazil When a patient has been controlled for many years, it is often appropriate to ask whether anticonvulsant treatment may safely been withdrawn. There are many considerations here, and individual patietn concern and preferences, including risk aversion, must be taken into account before a recommendation can be made. 16. Approach to the patient who fails the first drug, Derek J. Chong Seizures may continue to occur with medical treatment or the treatment may cause intolerable side-effects. Both are considered failures. The main choice to consider is substitution with another agent in monotherapy versus dual therapy. 17. Drug-drug interactions: AEDs, Derek J. Chong Many AEDs have effects on the each other due to changes in liver enzymes and protein binding particularly of the older generation. Pharmacodynamic effects, including interactions at the level of the receptor, can be important in neurotoxic side-effects, and may play a role in polytherapy efficacy as well. 18. Drug-drug interactions: others, Derek J. Chong Enzyme-inducing medications include phenytoin, carabamazepine and phenobarb, and to a lessor extent oxcarbazepine and topiramte. Significant interactions occur with frequently concomitantly used medications such as oral contraceptives, coumadin. 19. Treating epilepsy in pregnant or lactating women, Daniel Friedman AEDs pose particular difficulties in pregnant women including teratogenicity and altered metabolism. Many drugs are also excreted in breast milk though most women with epilepsy are able to successfully breast feed. 20. Treating seizures in the elderly, Derek J. Chong Single and recurrent seizures are common in the elderly population. Acute symptomatic seizures are less likely to turn into epilepsy, and longterm treatment is often not indicated. In other situations, treatment is important to reduce the sequelae of seizures, which could cause significant injury. Tolerability is the most important consideration, as many AEDs have the potential to worsen other common medical issues of the elderly. Section 3: Treatment Considerations: Surgery and other treatments 21. Refractory epilepsy: general approach, Carl W. Bazil Patients with epilepsy who have failed two trials of an appropriate anticonvulsant drug should be considered for further evaluation. Usually, this includes video-EEG monitoring to confirm the diagnosis, as a substantial subset will be found to have conditions other than epilepsy. If epilepsy in confirmed, the patient may be considered for other treatments including alternative medications, devices, and surgery. 22. Refractory idiopathic generalized epilepsy, Daniel Friedman Patients with idiopathic generalized epilepsy who have continued seizures despite appropriate antiepileptic drugs should undergo a trial of valproate which may be the most effective agent in these epilepsies. Video-EEG monitoring is recommended for patients with continued seizures as careful analysis may reveal a focal epilepsy. 23. Refractory localization related epilepsy: Extratemporal epilepsy, Carl W. Bazil In refractory patients who have extratemporal onsets, surgical treatment is often more complicated. These patients still have a higher chance of cure with surgery than with additional medication trials. In addition to routine video-EEG monitoring and MRI, further imaging studies such as PET or SPECT scans may help to localize onset. Intracranial electrode implantation followed by video-EEG monitoring is often required to definitively localize seizure onset and distinguish from eloquent cortex with brain mapping. 24. Alternative treatments and the ketogenic diet, Derek J. Chong Numerous patient surveys have shown an increase in the use of complementary and alternative therapies, up to 25% in epilepsy. Diet as an alternative therapy for seizures has been effective for many patients, while botanicals, biofeedback and other approaches show promise, but have not yet been proven or standardized. Being open-minded but exercising caution may be the best approach for the neurologist. Section 4: Prognostic, Social, and Behavioral Issues 25. Depression in epilepsy, Daniel Friedman Depressive symptoms are common in patients with epilepsy and occur at much higher rates than in the general population. Patients with epilepsy have higher rates of suicide as well. Identifying and treating mood disorders can improve the quality of life for epilepsy patients. 26. Psychosis and seizures, Carl W. Bazil Psychosis can rarely occur transiently in the immediate postictal period; this is usually transient but can result in injury. More difficult from a diagnostic standpoint may be postictal psychosis, as this may begin days after a seizure. In cases of unusual or refractory psychosis, consideration should be given to the possibility of unrecognized seizures causing or exacerbating psychosis. 27. Cognitive and behavioral issues, Carl W. Bazil Two of the most common complaints in patients with epilepsy are mood problems and difficulty with cognition. Both have numerous possible causes, but treatment choices in patients with epilepsy should always be made with these in mind. 28. Sleep disturbances in epilepsy, Carl W. Bazil Quality sleep is important for everyone, but is particularly important in patients with epilepsy. Sleep disruption from any cause can contribute to the intractability of epilepsy, and can also cause drowsiness, inattention, and apparent memory dysfunction. Vigilance for coexisting sleep disorders is an important aspect of epilepsy care. 29. Bone health, Derek J. Chong Reduced bone density has been shown to be a significant co-morbidity for patients with epilepsy. Thus far, it seems that enzyme-inducing medications have the greatest risk for causing problems with bone health. Substitution of the potentially offending agent is likely necessary. Repletion of vitamin D through supplementation appears safe, though it is not known what will be the most effective treatments. 30. Sudden unexplained death in epilepsy, Daniel Friedman Patients with epilepsy have a much higher rate of unexpected sudden death compared to the general population. Patients with poorly controlled epilepsy and frequent tonic-clonic seizures are at particular high risk. 31. Work, driving, and epilepsy, Carl W. Bazil Safety is of primary importance in patients with epilepsy. This is particularly concerning with driving, and in work or other activities that may place the patient (and potentially others) at risk should a seizure occur. The risk of seizure recurrence must be considered on an individual basis before recommendations can be made, however general guidelines are also helpful in discussing this topic with patients.

About the Author

Carl W. Bazil, MD, PhD, Caitlin Tynan Doyle Professor of Clinical Neurology, Director, Division of Epilepsy and Sleep, Department of Neurology, Columbia University, New York, NY. Derek Chong, MD, Assistant Professor of Clinical Neurology, Director, Clinical Anticonvulsant Drug Trials, Department of Neurology, Columbia University, New York, NY. Daniel Friedman, MD, Assistant Professor of Neurology, Department of Neurology, New York University, New York, NY.

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