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In the Clinic Epilepsy © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. What are the symptoms of epilepsy? Sensory: numbness, tingling, pain Motor: twitching, jerking, rhythmic or semirhythmic uncontrolled movements Psychic: fear, sadness, elation, laughing Automatic: lip smacking, chewing, swallowing Loss of tone, incontinence, and tongue biting Staring or repetitive blinking Altered awareness, impaired ability to interact normally Individual may be unaware seizure has occurred © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. Elements of history and physical History How do you know that a seizure is going to occur? What's the first thing that happens? Then what? Do you have any other intermittent movements or feelings that occur without an apparent cause? Physical exam Look for focal findings Presence of intracranial structural disturbance? Blurred disc margins on an ocular exam? intracranial mass lesion may be increasing intracranial pressure Hemiatrophy of a limb or digit? suggests incomplete contralateral cerebral development © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. Seizure evaluation First seizure History and physical examination Labs: glucose level, chemistry panel, liver function tests, BUN:creatinine, pregnancy test, CBC, toxicology, alcohol level Lumbar puncture if febrile, nuchal rigidity, immune compromise Electroencephalogram; CT or MRI Consider HIV test Breakthrough seizure History and physical examination Labs: As above, plus trough anticonvulsant levels Neuroimaging if new type or semiology or frequency changes EEG if patient does not return to baseline © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. Differential diagnosis Syncope from vascular insufficiency, anemia, cardiac dysrhythmias, hypovolemia, autonomic dysfunction Conditions that may cause altered awareness, repetitive or stereotyped movements, impaired cognitive function Sleep disturbances; Metabolic derangements Movement disorders; Migraine Delirium or dementia Psychiatric and psychological conditions Panic attacks, PTSD, pseudoseizures May be difficult to distinguish from epileptic seizures © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. What tests should be done to diagnose epilepsy? EEG Routine Ambulatory outpatient or inpatient: if symptoms occur frequently or can be provoked by reproducible situations Cardiac testing Routine ECG or ambulatory cardiac monitoring Echocardiography Neuroimaging Focal or space-occupying lesions Migrational disorders or vascular lesions © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. Do patients with epilepsy have related comorbidities? Pneumonia, asthma, upper GI bleeding Hormonal imbalances Reproductive endocrine disorders Perimenstrual or periovulatory seizures or seizures during entire second half of the menstrual cycle Low sexual function among men Cognitive impairment Mood disorders (depression, anxiety) Anticonvulsants can have adverse effects that exacerbate concomitant medical conditions © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. CLINICAL BOTTOM LINE: Diagnosis... Careful history and physical exam Neuroimaging with MRI Ambulatory or continuous EEG monitoring Many comorbidities are associated with epilepsy From etiologic cause or from treatments for the condition Proper identification and management of these may improve functioning and quality of life © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. How can epilepsy be prevented? Identify and avoid seizure triggers Soon after a seizure, patients should record events over the past 24 h to identify possible patterns Insufficient sleep or alcohol use may trigger seizures Counsel on ways to improve sleep duration and quality and on ways to avoid or limit alcohol use Impaired absorption of seizure medications (GI illness, colonoscopy prep) may result in seizure Intermittent use of short-term benzodiazepines may prevent progression into status epilepticus © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. CLINICAL BOTTOM LINE: Prevention... No proven strategies to avoid the development of epilepsy Careful history may identify triggers that can be avoided Sleep deprivation Use of alcohol Planned or inadvertent nonadherence to medication Providing patients with small quantity of low-dose oral benzodiazepines may decrease the risk of recurrent seizures in the setting of intercurrent illness © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. How should epilepsy be treated initially? Treatment typically initiated after the second seizure Prescribe pharmacotherapy >2 dozen anticonvulsants FDA-approved for epilepsy Identify ones with efficacy in the patient's type of epilepsy Consider potential adverse effects, interactions with other medical conditions or medications, plans for childbearing Consider time to reach optimal dosing and dosing schedule Consider other lifestyle factors No evidence supports using one over another where both medications have efficacy in epilepsy syndrome/seizure type © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. Offer strategies for taking medication consistently If patients don’t respond to the first agent or have unacceptable adverse effects, try a second agent Either as an adjunct to the first Or cross-taper to allow for resultant monotherapy Once effective dose is established, document serum concentration If seizures continue while receiving 2 anticonvulsants: Refer to a neurologist or a specialty center © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. What are the adverse effects of epilepsy treatment? Fatigue, dizziness, blurred vision, incoordination, gait imbalance Tend to be dose-dependent rather than idiosyncratic May be alleviated with slower dose-escalation plan or by taking the medication on full stomach Increased tendency to suicidality As early as 1 week after initiation of treatment FDA warning: physicians must warn patients of risk for suicidality and screen for depression or suicidality at regular intervals during dose escalation © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. Are there devices to treat epilepsy? Vagus nerve stimulator Generator implanted subcutaneously in anterior chest wall or axilla Lead is threaded subcutaneously from generator to left vagus nerve Provides regular electrical impulses and can also deliver impulses through external hand-held magnet Responsive neurostimulation system Stimulator implanted in the skull Leads extend from generator to surface of the brain or into the brain parenchyma where seizures originate Can be programmed to respond to seizures directly, sending electrical impulses to the seizure focus or foci © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. What is the role of surgery? For patients who have failed ≥ 2 anticonvulsants or have intolerable adverse effects Refer to epilepsy center where the surgery may be done Risks: wound infections, meningitis, hemorrhagic complications, neurologic deficits Transient postsurgical psychiatric disturbance may occur 2/3 of patients with specific resections become free of all but simple partial seizures Anticonvulsants may be reduced or withdrawn if patients become seizure-free But risk for subsequent relapse is higher if all anticonvulsant therapy is stopped © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. Is there a role for hormonal treatment of epilepsy? Exogenously administered hormonal treatment For women with hormonally-sensitive seizures, Mitigates hormonal oscillations that trigger events May improve seizure control without additional anticonvulsant therapy Requires extensive recordkeeping to identify a catamenial pattern of events Serial blood work needed to identify hormonal changes © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1. CLINICAL BOTTOM LINE: Treatment... Many anticonvulsants are available for initial treatment If ≥ 2 fail in a patient, refer to neurologist or epilepsy center to consider treatment options: Implantable devices Resective or minimally invasive surgery For women with catamenial epilepsy, hormonal manipulation © Copyright Annals of Internal Medicine, 2016 Ann Int Med. 164 (2): ITC2-1.