Loading…

Flash Player 9 (or above) is needed to view presentations.
We have detected that you do not have it on your computer. To install it, go here.

Like this document? Why not share!

Clinical Case Studies in Epilepsy

on

  • 5,809 views

 

Statistics

Views

Total Views
5,809
Views on SlideShare
5,809
Embed Views
0

Actions

Likes
0
Downloads
156
Comments
0

0 Embeds 0

No embeds

Accessibility

Categories

Upload Details

Uploaded via as Adobe PDF

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

Clinical Case Studies in Epilepsy Clinical Case Studies in Epilepsy Document Transcript

  • ® NEUROLOGY BOARD REVIEW MANUAL STATEMENT OF EDITORIAL PURPOSE Clinical Case Studies inThe Hospital Physician Neurology Board ReviewManual is a peer-reviewed study guide for Epilepsyresidents and practicing physicians preparingfor board examinations in neurology. Each Editor:manual reviews a topic essential to the cur- Alireza Atri, MD, PhDrent practice of neurology. Instructor in Neurology, Harvard Medical School, Assistant in PUBLISHING STAFF Neurology, Memory Disorders Unit, Massachusetts General Hospital, PRESIDENT, GROUP PUBLISHER Boston, MA Bruce M. White EDITORIAL DIRECTOR Contributor: Debra Dreger Tracey A. Milligan, MD ASSOCIATE EDITOR Instructor in Neurology, Harvard Medical School, Director, Faulkner Rita E. Gould Hospital Epilepsy/EEG, Associate Neurologist, Brigham and Women’s EDITORIAL ASSISTANT and Faulkner Hospitals, Boston, MA Farrawh Charles EXECUTIVE VICE PRESIDENT Barbara T. White EXECUTIVE DIRECTOR OF OPERATIONS Jean M. Gaul Table of Contents PRODUCTION DIRECTOR Suzanne S. Banish Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 PRODUCTION ASSISTANT Kathryn K. Johnson Evaluation of a First Seizure. . . . . . . . . . . . . . . . . . . . . . . 2 ADVERTISING/PROJECT MANAGER Patricia Payne Castle Diagnosis and Treatment of Epilepsy in the Elderly . . . . . 6 SALES & MARKETING MANAGER Deborah D. Chavis Management of Epilepsy in Pregnancy . . . . . . . . . . . . . . . 8 NOTE FROM THE PUBLISHER: Acute Mental Status Change in a Patient with Epilepsy . . 11 This publication has been developed without involvement of or review by the American Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Board of Psychiatry and Neurology. References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Endorsed by the Association for Hospital Medical Education Cover Illustration by Kathryn K . JohnsonCopyright 2006, Turner White Communications, Inc., Strafford Avenue, Suite 220, Wayne, PA 19087-3391, www.turner-white.com. All rights reserved. No part of thispublication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, electronic, photocopying, recording, or oth-erwise, without the prior written permission of Turner White Communications. The preparation and distribution of this publication are supported by sponsorshipsubject to written agreements that stipulate and ensure the editorial independence of Turner White Communications. Turner White Communications retains fullcontrol over the design and production of all published materials, including selection of appropriate topics and preparation of editorial content. The authors aresolely responsible for substantive content. Statements expressed reflect the views of the authors and not necessarily the opinions or policies of Turner WhiteCommunications. Turner White Communications accepts no responsibility for statements made by authors and will not be liable for any errors of omission or inac-curacies. Information contained within this publication should not be used as a substitute for clinical judgment.www.turner - white.com Neurology Volume 10, Part 1 1
  • NEUROLOGY BOARD REVIEW MANUAL Clinical Case Studies in Epilepsy Tracey A. Milligan, MD Gastaut syndrome, myoclonic epilepsies), idiopathicINTRODUCTION partial epilepsy syndromes (eg, benign epilepsy with centrotemporal spikes), idiopathic generalized syn- A seizure is a temporary alteration in brain function dromes (eg, benign neonatal convulsions, juvenile myo-due to excessive and/or hypersynchronous neuronal clonic epilepsy [JME]), and special syndromes such asactivity. Epilepsy is the tendency to have recurrent unpro- febrile seizures. A specific epilepsy syndrome may re-voked seizures. Approximately 10% of individuals will quire specific anticonvulsant drug treatment and is fre-have 1 seizure in his or her lifetime, and up to 3% will quently associated with a predictable prognosis. Thesuffer from epilepsy.1 However, the prevalence of active ILAE is currently developing a third diagnostic schemeepilepsy is only 0.8%. In the United States, approxi- aimed at providing a standardized description of indi-mately 2 million people have epilepsy, with 100,000 new vidual patients rather than a fixed classification.8 Thiscases diagnosed per year. People of every background scheme uses 5 axes: ictal phenomenology (axis 1); sei-and age are affected. Epilepsy is associated with im- zure type (axis 2); syndrome, when known (axis 3);paired quality of life, and its treatment can have serious genetic defect or specific pathologic substrate for symp-consequences. Unfortunately, 20% to 40% of patients tomatic focal epilepsies (axis 4); and impairment classi-with epilepsy continue to experience occasional sei- fication (axis 5).zures despite treatment.2 – 5 This review presents 4 cases that evolve over the Epilepsy is not a single condition but a symptom of course of the discussion to encompass evaluation of avarious disorders and reflects underlying brain dysfunc- first seizure, diagnosis and management of epilepsy intion. The International League Against Epilepsy (ILAE) the elderly, management of epilepsy during pregnancy,currently has 2 classification schemes for epilepsy that and evaluation and management of acute mental statusare designed to be used together. The first divides sei- change in a patient with epilepsy.zures into 3 types, with subtypes of each: partial (focalseizures involving only part of the brain), generalized(seizures involving both hemispheres of the brain), and EVALUATION OF A FIRST SEIZUREunclassifiable (Table 1).6 This system allows for simpleclassification that may determine diagnostic evaluation,choice of medication, and prognosis. A supplement to CASE 1 PRESENTATIONthis system, the ILAE Classification of Epilepsies and A 19-year-old woman is referred to a neurologist forEpileptic Syndromes,7 divides epilepsies into 4 groups: evaluation after experiencing a convulsion while jog-localization-related (involves 1 or more focal areas of ging. The patient is otherwise healthy and takes nothe brain), generalized (involves both hemispheres of medications besides oral contraceptives. Records fromthe brain at the same time), undetermined, and special the emergency department (ED) visit document that asyndromes. The localized and generalized groups fur- physician who was jogging behind the patient witnessedther divide into idiopathic (no identifiable cause and no the event and did not notice any prodrome or focalassociated neurologic abnormalities, although underly- findings. Evaluation in the ED showed a postictal peri-ing genetic mutations are increasingly being discov- od of confusion for 20 minutes followed by a normalered), symptomatic (cause is identified), or cryptogenic examination. Electrolytes, renal function, complete(presumed symptomatic, but the cause is unknown) epi- blood count, and a computed tomography (CT) scanlepsy syndomes. Epilepsy syndromes are defined by the of the patient’s head were normal.specific seizure type, clinical findings (including age ofonset), and type of EEG abnormality. Epilepsy syn- DIAGNOSING EPILEPSYdromes include the catastrophic epilepsy syndromes ofinfancy and childhood (eg, West syndrome, Lennox- • What is the differential diagnosis for a seizure?2 Hospital Physician Board Review Manual www.turner - white.com
  • Clinical Case Studies in EpilepsyTable 1. 1981 ILAE Classification of Epilepsy Table 2. Nonepileptic Disorders That Mimic EpilepsyPartial (focal, local) seizures Syncope (vasovagal/neurocardiogenic, decreased cardiac Simple (consciousness not impaired): motor, somatosen- output, volume depletion, arrhythmia) sory, autonomic, psychic Migraine (classic, basilar, confusional, acephalgic) Complex (impairment of consciousness): simple partial Cerebrovascular (transient ischemic attack, amyloid evolving to impaired consciousness or impaired con- angiopathy) sciousness at onset Sleep disorders (REM behavior disorder, narcolepsy, Partial seizures evolving to GTC parasomnias) Simple to GTC Movement disorders (tics, nonepileptic myoclonus, tremor) Complex to GTC Transient global amnesia Permission to electronically reproduce this Simple to complex to GTC copyright holder. table not granted by Psychiatric (panic, dissociation, conversion, malingering)Generalized seizures (convulsive or nonconvulsive) REM = rapid eye movement. Absence (including atypical absences) Myoclonic results from a recognizable cause. A seizure can be pro- Clonic voked by many factors (Table 5). Common causes in- Tonic clude metabolic disturbances, medications, and alcohol Tonic-clonic withdrawal. If seizures recur only in the presence of this Atonic (astatic) stimulus, they are not defined as epilepsy.Unclassified epileptic seizures • What are important historical questions to ask the patient and/or any witness to the event?GTC = generalized tonic-clonic; ILAE = International League AgainstEpilepsy. (Adapted with permission from Proposal for revised clinicaland electroencephalographic classification of epileptic seizures. From Questions for the Patientthe Commission on Classification and Terminology of the International Asking the patient about events leading up to the sei-League Against Epilepsy. Epilepsia 1981;22:489–501. Copyright © 1981Blackwell Publishing Ltd.) zure may reveal possible provoking factors (eg, stress, alcohol withdrawal, sleep deprivation, medication use, illicit drug use) or unusual stimuli (eg, hyperventilation,Distinguishing Between Epileptic and Nonepileptic flickering lights). The patient should also be asked toSeizures identify, if possible, any activity that immediately preced- The first step in evaluating a seizure is to determine ed the event (eg, exercise, change in posture). A reviewwhether the event was an epileptic seizure or a paroxys- of the early symptoms as well as postictal symptomsmal event mimicking an epileptic convulsion (Table 2). (eg, presence of a Todd’s paralysis) may also help classifySyncope is commonly mistaken for an epileptic seizure; the event.however, certain features can help distinguish between Obtaining a history of any prior events suspicious forthe 2 types of events (Table 3). An electroencephalo- seizures also is important and may lead to a diagnosis ofgram (EEG) during an event can be helpful. Convulsive previously unrecognized epilepsy. Suspicious events in-syncope involves the release of brainstem and spinal clude episodes of lost time, frequent déjà vu, transientactivity from cortical influence, and the EEG shows neurologic symptoms, morning myoclonus, awakeningslowing and flattening rather than seizure activity. An with a tongue bite or incontinence, nocturnal convul-event that occurs while exercising may be more suspi- sions, and reports of unusual movement that the patientcious for a cardiac etiology. Psychogenic nonepileptic was unaware of performing, such as staring with eye flut-seizures (PNES, or pseudoseizures) are also frequently tering, lip smacking, or hand automatisms.mistaken for epileptic seizures and represent up to 20%of referrals to an epilepsy center. Certain features aid in Questions for a Witnessthe diagnosis of PNES (Table 4), although inpatient Obtaining a history from any witness to the event isvideo EEG monitoring may be required. also critical in making the diagnosis. Key questions to ask Once an event has been identified as a seizure, the a witness include: Where in the body did the movementsnext step is to determine whether the seizure was pro- begin? Did the patient’s head or eyes deviate to onevoked. This distinction has important therapeutic and side? Were there automatisms of the face or hands? Didprognostic implications. A provoked seizure is one that incontinence or tongue biting occur? What were thewww.turner - white.com Neurology Volume 10, Part 1 3
  • Clinical Case Studies in EpilepsyTable 3. Features That Distinguish Syncope from Table 5. Common Causes of Provoked SeizuresSeizure Metabolic (hyponatremia, hypoglycemia, hyperthyroidism,Clinical nonketotic hyperglycemia, hypocalcemia, hypomagnesemia,Feature Syncope Seizure renal failure, porphyria)Loss of con- Typical Common Hypoxia sciousness Medications (benzodiazepine withdrawal, barbiturate with-Episode duration Seconds Minutes drawal, phenothiazines, buproprion, tramadol)Involuntary Common Typical Substance abuse (alcohol withdrawal, cocaine, amphetamine, movements phencyclidine, methylenedioxymethamphetatime [“ecstasy”])Triggers Frequent RarePreceding symp- Nausea, blurred Sensory, motor, features of the postictal state? The patient’s level of toms vision, feeling psychic auras hot, tinnitus, responsiveness and awareness will also help classify the palpitations seizure and has important implications for possible eti- ologies, diagnostic work-up, treatment, and prognosis.Postictal features Amnesia for Amnesia for event event, somno- plus confusion, • What historical features are considered risk factors lence, headache somnolence, for the development of epilepsy? headacheEEG findings Slow waves, flat- Focal or general- RISK FACTORS FOR EPILEPSY tening ized spike-wave There are well-recognized risk factors for the develop-EEG = electroencephalogram. ment of epilepsy (Figure 1).9 Febrile seizures occur in 2% to 4% of otherwise healthy children younger than age 5 years; however, a history of a complex febrile seizure or a neurodevelopmental abnormality or a family history ofTable 4. Features That Distinguish Psychogenic epilepsy may increase the risk of developing epilepsy toNonepileptic Seizures (PNES) from Tonic-Clonic 2% to 4%.10 A history of significant head trauma also is aEpileptic Seizures (ES) risk factor. Studies of Vietnam War veterans show a risk of 50% after a penetrating head trauma.11 Head trauma withClinical loss of consciousness, amnesia, or a skull fracture increas-Feature PNES ES es the 5-year risk to approximately 2%; however, the riskTrigger Rare is increased with severe head injuries, with 12% of sur- Frequent vivors developing epilepsy.12 Vascular lesions are a signifi-Onset Often gradual Usually sudden cant cause of epilepsy. Epilepsy develops in 6% to 44% ofMovements May stop and Usually synchro- individuals with arteriovenous malformations.13 Cavern- start, pelvic nized and ous malformations commonly present as seizures,14 and thrusting, back stereotyped cerebrovascular disease is the major cause of epilepsy in arching, erratic the elderly.1 Brain tumors account for approximately 4% movements, absence of of cases of epilepsy,10 and seizures are often the presenting stereotypy feature of brain tumors. Central nervous system (CNS)Eyes Open infections can also increase the risk of developing epilep- Closed sy, particularly in children and the elderly. This risk is fur-Lateral tongue bite Rare Common ther increased with certain types of infections and if thereSelf-injury Rare Common are symptomatic seizures early in the course of infection.Incontinence Rare Common For example, in patients with viral encephalitis and earlyPostictal confusion Rare Common seizures, the risk of epilepsy is 10% by 5 years and 22% byDuration Lengthy (hours) 1–2 min 20 years.15 Degenerative CNS diseases are associated withSerum prolactin Usually elevated an increased risk of epilepsy. Alzheimer’s disease increas- Usually normal es the risk tenfold, and 10% of long-term Alzheimer’s dis- ease survivors eventually develop epilepsy.1 Up to 5% of patients with multiple sclerosis develop epilepsy.16 Mental4 Hospital Physician Board Review Manual www.turner - white.com
  • Clinical Case Studies in Epilepsy Traumatic brain injury Severe Moderate Mild N/S CNS infection Figure 1. Relative risk of epilepsy (log Encephalitis Bacterial meningitis scale), shown by cause. CNS = central Aseptic meningitis N/S nervous system; N/S = not statisticallyCerebrovascular disease significant. (Adapted with permission from Annegers JF, Rocca WA, Hauser Alzheimers disease WA. Causes of epilepsy: contributions of Febrile convulsions the Rochester epidemiology project. Simple Complex Mayo Clin Proc 1996;71:572.) Family history Mental retardation/ cerebral palsy 0.5 1 5 10 30 Relative riskretardation (MR) and cerebral palsy (CP) are important and she may drop what she is holding. The patientrisk factors for the development of epilepsy in children reports that her father has had 2 unprovoked convul-and young adults. Prematurity and birth complications sions during adulthood and is currently taking pheny-are risk factors for both CP and MR, but pre- or perinatal toin. She has no other known risk factors for epilepsy.events themselves are not independent risk factors for In consideration of the patient’s history of photosensi-epilepsy when children with CP or MR are excluded.17 tive absence seizures, morning myoclonic seizures, andFinally, patients with a first-degree relative with epilepsy 1 convulsive seizure, the neurologist make a presump-have a twofold to fourfold risk of developing epilepsy.18 tive diagnosis of JME.Risk of a Recurrent Seizure • What are characteristic features of JME? Assessing risk of seizure recurrence is important in JME is an idiopathic generalized epilepsy (IGE) syn-the counseling and management of patients (Table 6). drome characterized by myoclonic jerks (particularly inAfter a single tonic-clonic seizure, the 5-year recurrence the morning) and generalized tonic-clonic seizures; 28%rates vary from 16% to 62%, depending on the presence of affected persons also have absence seizures—a type of gen-of other risk factors. The greatest risk of recurrence is eralized seizure that can occur in both idiopathic andwithin the first 6 months.19 A family history of seizure, a symptomatic, generalized epilepsy. IGEs make up approx-spike-and-wave pattern on EEG, and a history of prior imately one third of all epilepsies, and different IGEneurologic insult increase the risk of recurrence after a syndromes frequently cluster within a family. They arefirst unprovoked seizure.20 An abnormal EEG may be a considered to be primarily genetic in origin. JME is ansignificant risk factor for recurrence (58%–75% versus inherited disorder, although in most cases the exact mode16%–27% in cases of a normal EEG).21–24 However, a of inheritance is unclear. Between 17% and 49% ofsingle EEG is normal in approximately 50% of persons patients with JME have a relative with epilepsy. The genet-with epilepsy.25 Other risk factors for recurrence may ics of IGEs was recently reviewed.27 Mendelian or mono-include a family history of epilepsy (46% versus 27%), genic IGEs are often ion channel disorders. The moreTodd’s paralysis (75% versus 39%), partial seizures, and common familial IGEs are complex and nonmendelian.an abnormal neurologic examination.26 There has been considerable progress in identifying many of the genetic mutations responsible for epilepsyCASE 1 CONTINUED that can result in a similar electroclinical syndrome. The patient reports that for as long as she can re-member flashing lights (eg, riding in the car and seeing CASE 1 CONTINUEDthe lights flash through the trees) have caused her to The patient’s physical and neurologic examinationslose short periods of time. As a result, she avoids jogging are normal. An EEG is performed, which shows occa-through areas with leafy trees on sunny days. She also sional 4- to 6-Hz spike-wave discharges. Results of mag-notes that in the morning her hands occasionally jerk netic resonance imaging (MRI) are normal.www.turner - white.com Neurology Volume 10, Part 1 5
  • Clinical Case Studies in EpilepsyTable 6. Risk Assessment After a First Seizure Table 7. Commonly Used Antiepileptic DrugsHistory: Previously undiagnosed seizures, possible provoking Partial seizures (± secondary generalization) factors, focal onset or aura, risk factors for epilepsy Carbamazepine LevetiracetamExamination: Presence of focal neurologic signs, cognitive or Phenytoin Oxcarbamazepine developmental disorder, unrecognized medical disease Primidone TopiramateLaboratory tests: Tailored depending on patient’s age and Felbamate Tiagabine presenting scenario: glucose, sodium, calcium, magnesium, liver and kidney function, complete blood count, blood and Lamotrigine Zonisamide urine toxicology, thyroid function tests; also, lumbar punc- Gabapentin ture if suspicion of meningitis or encephalitis or cancer known to metastasize to the meninges Generalized seizuresMagnetic resonance imaging: Coronal cuts through the mesial Absence Tonic-clonic temporal lobe structures to assess for mesial temporal Ethosuximide Valproate sclerosis, gradient echo sequence to assess for cavernous Valproate Phenytoin malformations Lamotrigine CarbamazepineElectroencephalogram: Should include both a sleep and waking recording; a sleep-deprived or ambulatory record- Topiramate Felbamate* ing may increase the yield in assessing for epileptiform Levetiracetam Lamotrigine abnormalities Myoclonic Topiramate Valproate Levetiracetam Clonazepam Zonisamide• Based on the patient’s EEG reading, how should she Lamotrigine be managed? Topiramate An EEG showing generalized fast spike-wave dis- Levetiracetamcharges confirms the diagnosis of JME. The diagnosis of Zonisamidegeneralized versus focal epilepsy is important, as someAEDs that are helpful in focal epilepsies may worsen Adapted with permission from American Epilepsy Society. Clinical epi-aspects of IGE. The efficacy of AEDs also differs depend- lepsy. Available at www.aesnet.org/visitors/professionaldevelopment/ing on the type of generalized seizure. Most seizures re- meded/newppt/clinical/clinical13-20.pdf. Accessed 4 Jan 2006.spond well to appropriate AEDs, but treatment is often *For tonic-clonic seizures associated with Lennox-Gastaut syndrome.life-long. Commonly used AEDs are listed in Table 7. For JME, valproate is effective at fairly low doses.Lamotrigine may be preferable in women of childbear- begin with the patient suddenly stiffening, falling to theing age, given the birth defects associated with val- ground, and shaking for 1 to 2 minutes, after which sheproate. Many AEDs, including benzodiazepines, carba- is confused for 10 to 45 minutes. The daughter reportsmazepine, phenobarbital, primidone, oxcarbazepine, that these episodes occur 1 to 2 times a week. On eval-and topiramate, affect oral contraceptives. Lower serum uation today, the patient’s neurologic examination islevels of lamotrigine are associated with concomitant normal, but her blood pressure is 190/90 mm Hg.use of oral contraceptives. Thus, if lamotrigine therapyis chosen for the case patient, a higher dose than oth- • What is the differential diagnosis of transient spellserwise is required may be necessary. in elderly patients? DIFFERENTIAL DIAGNOSISDIAGNOSIS AND TREATMENT OF EPILEPSY IN The basic differential diagnosis of transient spells ofTHE ELDERLY neurologic dysfunction or loss of consciousness in the elderly includes cardiac events, transient ischemic at- tacks (TIAs), amyloid angiopathy, migraine, and sei-CASE 2 PRESENTATION zures. Other etiologies to consider include parasom- A 70-year-old woman is referred to a neurologist for nias, movement disorders, metabolic dysfunction, andevaluation of recurrent episodes of loss of conscious- psychogenic events.ness. According to the patient’s daughter, the episodes Cardiovascular disorders that may impair cerebral6 Hospital Physician Board Review Manual www.turner - white.com
  • Clinical Case Studies in Epilepsyblood flow and cause spells include arrhythmias, con-gestive heart failure, and aortic stenosis. Orthostatichypotension, precipitated by volume depletion and/orantihypertensive or diuretic medications, can also leadto syncope. TIAs have characteristic symptoms and Permission to electronically reproduce thissigns consistent with known vascular territories. They figure not granted by copyright holder.typically have negative symptoms (eg, weakness, senso-ry loss), whereas seizures are associated with positivephenomena (eg, stiffening, shaking, positive sensorydisturbances, hallucinations). Limb shaking TIAs arean exception, with shaking of an arm, leg, or bothcaused by severe carotid stenosis. The underlying Figure 2. Age-specific incidence of seizures in Rochester, MN,pathophysiology of cerebral amyloid angiopathy spells between 1935 and 1984. (Adapted with permission from Hauserhas not been definitively established, but their presen- WA, Annegers JF, Kurland LT. Incidence of epilepsy and unpro-tation is similar to that of TIAs. Migraine auras and voked seizures in Rochester, Minnesota: 1935–1984. Epilepsiaother migraine symptoms may precede the headache 1993;34:456. Copyright © 1993 Blackwell Publishing Ltd.)by more than an hour, and “migraine equivalents” with-out headache are common in the elderly. Migraineauras are more gradual in onset and of longer duration older than age 60 years include cerebral infarction (33%than seizures. of cases), arteriosclerosis (15%), head trauma (7%), and hemorrhage (2%); other causes (eg, brain tumor, trau-CASE 2 CONTINUED ma, Alzheimer’s disease) account for 19% of cases, and Further history reveals that several times a week the in 24% of cases the cause is unknown.28 The risk factorspatient experiences episodes during which she smacks for development of post-stroke epilepsy are similar toher lips, picks at her clothes and hair, and is not respon- those for acute symptomatic seizures in stroke (eg, hem-sive. Her medical history is significant for hyper- orrhage, cortical involvement, size of infarct).32 An acutecholesterolemia, hypertension, and anxiety. She takes symptomatic seizure increases the risk of developingatorvastatin and hydrochlorothiazide. Family history is post-stroke epilepsy; 35% of individuals with acute sei-significant for a brother who developed seizures in his zures will develop post-stroke epilepsy.33 Most cases of60s and then had a stroke. The patient has no other cryptogenic seizures are probably related to cerebrovas-known risk factors for epilepsy. cular disease, given the increased incidence of stroke risk factors (particularly hypertension but also hypercholes-• How common are seizures in the elderly? terolemia), coronary artery disease, and peripheral vas-• What are the common causes of seizures in this pop- cular disesase.21 After a cryptogenic seizure, even in the ulation? absence of a history of stroke, there is an increased risk for a subsequent stroke, with a relative risk of 2.89.34INCIDENCE AND ETIOLOGY OF SEIZURES IN THEELDERLY • Is epilepsy easily diagnosed in the elderly? The incidence of epilepsy is highest in those aged • What diagnostic studies are helpful?75 years or older (Figure 2). Nearly 25% of all personswith epilepsy are elderly, and of all new seizures, 25% to DIAGNOSING EPILEPSY IN THE ELDERLY50% occur in the elderly.28,29 Up to 18% of elderly nurs- The diagnosis of epilepsy in the elderly is often de-ing home residents have epilepsy.30 Status epilepticus is layed. Most seizures are complex partial seizures withmore common in the elderly and can carry a fatal prog- episodic periods of unresponsiveness or staring spells.nosis (30%–40% among those aged ≥ 60 years).31 New- However, clinical features may differ compared withonset epilepsy in the elderly should generally be con- younger patients; the primary presentation may consistsidered either cryptogenic or symptomatic. If a seizure of altered mental status, memory lapses, episodes of con-is generalized tonic-clonic, it was probably of focal on- fusion, or sudden loss of consciousness, and postictalset with rapid secondary generalization, although there confusion may be prolonged.28have been rare case reports of newly diagnosed prima- Routine interictal EEGs are unlikely to reveal epilep-ry generalized epilepsy in the elderly. tic discharges. In 1 study, the first EEG showed interictal Major causes of newly diagnosed epilepsy in patients discharges in 35% of patients with pre-existing epilepsywww.turner - white.com Neurology Volume 10, Part 1 7
  • Clinical Case Studies in Epilepsyand only 26% of patients with seizure onset after age tein binding, and altered gastrointestinal absorption.60 years.35 However, ambulatory EEG or video EEG Phenytoin and valproate are highly protein bound andmonitoring may increase the diagnostic yield by as much may lead to a higher free fraction in the elderly, con-as 50%, particularly when combined with electrocard- tributing to adverse events. Cognitive changes and gaitiogram monitoring.36,37 Several studies have shown the dysfunction are common side effects of many AEDs.utility of inpatient video EEG monitoring. In a study of These symptoms may be attributed to other known prob-94 patients, 46 had documented epileptic events and 27 lems, and the patient may not be able to recognize thesehad documented nonepileptic events that included syn- side effects.cope, cerebrovascular events, sleep disorders, and psy- As new-onset seizures in this age-group are readilychogenic events.38 controlled with modest dosages, the selection of an ini- Neuroimaging is essential in the evaluation of most tial AED for an elderly patient should consider tolera-new-onset seizures and is crucial in the work-up of a bility and potential drug-drug interactions and sidenew seizure in an elderly patient. Head CT should be effects as much as efficacy of the agent. The VA Coop-used in the acute emergency setting to exclude hemor- erative Study assessed the efficacy and tolerability ofrhage or a large mass. Otherwise, an MRI with gadolini- 3 AEDs (gabapentin [up to 1500 mg], lamotrigine [upum is the imaging modality of choice and should be per- to 150 mg], and carbamazepine [up to 600 mg]) forformed expeditiously in patients older than 40 years.39 new-onset seizures in patients older than 60 years.28MRI with coronal cuts through the mesial temporal There was no significant difference in efficacy amongstructures is helpful in assessing for mesial temporal scle- these agents. However, trial retention was a critical cri-rosis, and gradient echo sequences may identify micro- terion by which the AEDs were evaluated; carbamaz-bleeds associated with cerebral amyloid angiopathy, cav- epine was associated with significantly more adverseernous angiomas, and post-traumatic changes. In the events (27.3%) compared with gabapentin (17.4%) orVA Cooperative Study, only 18% of patients were found lamotrigine (10%). Several agents are recently recog-to have normal head CT scans; common findings were nized as being associated with an increased risk of osteo-stroke (42.6%) and encephalomalacia (9.1%).28 Other porosis (carbamazepine, phenobarbital, primidone,findings included tumors (1.5%), atrophy, small-vessel phenytoin). The selection of an AED in the elderly hasdisease, and hydrocephalus. Cerebral and cervical vas- been recently reviewed.41cular studies may be indicated in the work-up as well. Given the high risk of stroke in elderly patients with cryptogenic seizures, careful assessment and treatment ofCASE 2 CONTINUED risk factors for stroke should be part of the overall care. The patient undergoes an MRI, which reveals mild Thus, the management of the case patient should involvediffuse atrophy and white matter changes consistent treatment and close monitoring of her blood pressure.with small-vessel ischemic disease. Laboratory test re-sults and a routine EEG are normal. A 24-hour ambu-latory EEG shows multifocal epileptiform discharges, MANAGEMENT OF EPILEPSY IN PREGNANCYparticularly in the right frontal region.• What are important treatment considerations for this CASE 3 PRESENTATION patient? A 35-year-old woman with a seizure history presents to a neurologist for advice on becoming pregnant. AtANTIEPILEPSY DRUGS IN THE ELDERLY age 20 years, the patient had a secondarily generalized New-onset seizures in the elderly have a higher risk seizure and was diagnosed with a right parietal regionfor recurrence (up to 90%), in part because the sei- meningioma. She took carbamazepine for 5 years andzures are symptomatic or cryptogenic. Even if the MRI then was tapered off the medication. She had a secondand EEG are unrevealing, initiation of AED therapy convulsive seizure 3 months later. She again tapered offshould be strongly considered and treatment will likely carbamazepine 4 months ago and had her third unpro-be long-term. voked seizure. She has resumed taking carbamazepine. The average community-dwelling elderly person takes The patient would like to become pregnant within5 medications daily, and the average nursing home resi- the next year. She wants to know the risks of having adent takes 5 to 10.40 Elderly patients are also more sensi- seizure versus taking carbamazepine during pregnancy,tive to drug interactions and adverse events because they if she can safely discontinue taking carbamazepine, andhave reduced hepatic and renal clearance, reduced pro- if there are other methods for managing her epilepsy.8 Hospital Physician Board Review Manual www.turner - white.com
  • Clinical Case Studies in Epilepsy• What are important treatment considerations for wo- fivefold increase in major malformations, depending on men with epilepsy who wish to become pregnant? the agent. Polytherapy is associated with an even greater risk of fetal malformations, although the main offenderPREGNANCY AND EPILEPSY appears to be valproate.44 All the older AEDs are class C or Approximately 1 million women of childbearing age D. Valproate is particularly teratogenic and associatedin the United States have epilepsy, and 200,000 give with an increased risk of neural tube defects. Higher peakbirth each year. Women with epilepsy appear to have a levels may be more teratogenic, and use of the extendedgreater baseline risk of fetal malformations, which is release preparation is preferable. Neural tube defects arefurther increased by the use of AEDs. There is also an associated with exposure to valproate and carbamazepineincreased seizure frequency in 17% to 33% of preg- at a frequency of 1% to 2% and 0.5% to 1%, respectively.nancies. Nevertheless, 90% of women with epilepsy Minor congenital anomalies affect 7% to 15% of infantshave a normal pregnancy and a healthy baby, and al- exposed to AEDs, which represents a twofold increasethough the incidence of congenital malformations is over that in the general population. These anomaliesincreased, the actual incidence of major malformations principally involve the face and digits and include hyper-remains low (ie, 4%–6% versus 2%–3% in the general telorism, epicanthal folds, broad nasal bridge, elongatedpopulation). philtrum, and distal digital and nail bed hypoplasia. Recent studies have shown a much higher risk with val-Risk of Seizures During Pregnancy proate versus carbamazepine.43,45 The North American The increased frequency of seizures during preg- Pregnancy Registry (www.massgeneral.org/aed) is an on-nancy is due to several factors. During pregnancy, the going study with a primary goal of determining the fre-volume of distribution increases, and hepatic and renal quency of major malformations in infants exposed tometabolism of AEDs are increased. Changes in serum- AEDs during pregnancy. Recently released data show anbinding proteins also affect the free component of med- increased risk of major malformations with phenobarbitalications. The increased levels of both estrogen and pro- (relative risk, 4.2; 95% CI, 1.5–9.4]).46 Phenytoin hasgesterone also may influence seizure frequency during increased the risk of fetal cleft palate and heart disease. Itpregnancy. Estrogen, which peaks during the third tri- also is associated with the fetal hydantoin syndromemester, has been shown to be epileptogenic, decreasing (ie, growth deficiency, small head size, abnormalities ofthe seizure threshold. Conversely, progesterone has the nails and fingers, other minor malformations); intel-antiepileptic effects; many women have fewer seizures ligence is usually normal. However, longer-term studiesduring the luteal phase of the menstrual cycle. In addi- of neurodevelopment show higher rates of developmen-tion to hormonal changes, increased stress and de- tal delay and lower IQ scores in children with in uterocreased sleep during pregnancy are also likely to lower exposure to valproate47 and phenobarbital.48the seizure threshold. Finally, patient compliance with Information is gradually being acquired for the new-AEDs may be decreased because of concerns about er AEDs, and it has been proposed that there is a lowermedication effects on the fetus. risk of teratogenicity as pregnancy outcomes have gen- The risks of having a seizure during pregnancy erally been favorable and no consistent pattern of mal-include fetal hypoxia as a result of decreased placental formations has been observed. However, animal studiesblood flow or apnea during a seizure. The fetal heart on all the agents show fetal toxicities, and there is lessrate may also decelerate, which may persist for up to known about the teratogenicity of the newer AEDs in30 minutes after the seizure.42 If there is maternal trau- humans. The International Lamotrigine Pregnancyma during a seizure, the fetus is at risk of injury and Registry has reported a very low incidence of majorthere is a risk of placental abruption or miscarriage. malformations,49 but this low incidence may be in partOne prospective study found no association between related to the significant decline in lamotrigine serumfirst trimester seizure and major malformations, but the levels during pregnancy.95% confidence intervals (CI) were wide (0.1–2.9).43 Patient-Specific Decisions Regarding AED UseRisk of AED Use During Pregnancy Despite the known risks of many AEDs, treatment is Older evidence indicates that women with epilepsy better than uncontrolled seizure activity. Prior to concep-have an increased risk of fetal malformations, even with- tion, an evaluation of the clinical necessity of an AED andout AED use. Specific congenital abnormalities include optimization of therapy is ideal. If continued AED thera-cleft lip and palate and cardiac anomalies. First trimester py is required, achieving monotherapy at the lowest effec-use of a single AED may be associated with a twofold to tive dose reduces the risks of teratogenicity. An AED canwww.turner - white.com Neurology Volume 10, Part 1 9
  • Clinical Case Studies in Epilepsyoften be discontinued safely. However, there is a contin- clude supplementation with polyunsaturated fatty acids,ued risk of seizures in the presence of a structural lesion. progesterone therapy, transcranial magnetic stimulation,The case patient, who has a structural cerebral lesion and neurostimulator devices, and gamma knife surgery.whose previous attempt to taper off carbamazepine wasunsuccessful, is at increased risk for having a seizure. After CASE 3 CONTINUED2 unprovoked seizures, the risk of a recurrent seizure is The patient decides to remain on carbamazepine57% over 1 year and 73% over a 4-year period.50 and not pursue surgical options. She is concerned about whether epilepsy will make it more difficult for her to• What options besides AEDs are available to treat epi- become pregnant, and she asks whether she should do lepsy? anything in particular while trying to become pregnant.NONPHARMACOLOGIC TREATMENT OPTIONS • What are fertility issues in women with epilepsy?Surgery Overall, women with epilepsy have fewer children Candidates for resective surgery include those with a than women in the general population; they also have astructural lesion and those with medically refractory higher rate of menstrual cycle irregularities (includingpartial epilepsy (ie, persistent and disabling seizures anovulatory cycles), hormonal abnormalities, polycysticdespite use of 2 or more appropriate first-line anti- ovary syndrome, infertility, weight gain, hirsutism, andseizure medications at appropriate doses) who have sei- galactorrhea.52 Fertility rates may be 33% lower in wo-zures from a region of the brain that can be resected men with epilepsy.53 Folate has been shown to decreasewithout neurologic morbidity. For medically intractable the incidence of neural tube defects. Women of child-partial epilepsy, surgical resection of the focal cortex is bearing age with epilepsy should take folate daily re-often the most effective treatment for both adults and gardless of their desire to become pregnant because thechildren; anterior temporal lobectomy is the most com- neural tube is formed before most women realize theymon surgical procedure performed and renders ap- are pregnant. Screening for a family history of birthproximately 60% to 80% of patients seizure-free. Other defects may be helpful in leading to a recommendationtypes of brain surgery include multiple subpial transec- for prenatal genetic counseling.tions (used for eloquent areas of cortex) and corpuscallosotomy (used to reduce drop attacks). CASE 3 CONTINUED The patient returns to the neurologist’s officeVagal Nerve Stimulation 3 months later after just learning that she is pregnant. The vagal nerve stimulator was developed based on She is feeling well and has had no seizures. She asks whatthe observation that intermittent vagal nerve stimula- special management will occur during her pregnancy.tion reduced seizures in experimental animals. The She also wants to know if her baby is at risk for havingvagal nerve stimulator is approved by the U.S. Food and seizures and if she can breastfeed while on carbamaz-Drug Administration for the treatment of medically re- epine.fractory epilepsy in individuals older than 12 years.Approximately one third of those treated with vagal • How should this patient be counseled at this time?nerve stimulation have a greater than 50% reduction intheir seizure frequency.51 Use of the vagal nerve stimu- EPILEPSY MANAGEMENT IN PREGNANCYlator can be considered equally efficacious as the addi- Table 8 summarizes principles of epilepsy manage-tion of a second or third AED, with minor side effects of ment in pregnancy. It is recommended that women whoneck pain, hoarseness, and a brief cough associated become pregnant continue folate supplementation andwith activation of the stimulator.51 begin to take prenatal vitamins and calcium supple- ments. If the patient is on AED therapy, it may be neces-Other Therapies sary to increase the dosage; some AEDs require up to a The ketogenic diet is a high-fat, low-carbohydrate two- to threefold increase in dosage during pregnancy todiet developed to mimic the anticonvulsant effect of maintain the same serum levels. Monthly monitoring offasting known since biblical times. Diet modification, free and total AED levels also is recommended. Becausethrough the ketogenic or low glycemic index diet, can be of the increased risk of anomalies, a level II fetal surveyhelpful in reducing seizure frequency, particularly in chil- should be performed at 18 to 20 weeks’ gestation, withdren, but is very restrictive and too onerous for most careful attention to the face, CNS, and heart. Because ofadults. Other therapies under clinical investigation in- the increased risk of neural tube defects, offering a10 Hospital Physician Board Review Manual www.turner - white.com
  • Clinical Case Studies in Epilepsymaternal serum α-fetoprotein (MSAP) screening test is Table 8. Epilepsy Management in Pregnancyalso recommended. Performing an amniocentesis rou-tinely for α-fetoprotein is controversial, but it is more sen- Preconceptionsitive than MSAP. In the setting of a family history of Evaluate need for continued AED therapyneural tube defects or with the use of valproate or carba- Attempt to decrease pharmacotherapy to monotherapymazepine, it may be recommended. Taper AEDs to the lowest possible dose(s) There is an increased risk of spontaneous hemor- Establish the level of total and free AEDs necessary forrhage in newborns that was historically described in achieving good clinical controlwomen taking phenobarbital or primidone. This risk Review family history for birth defects and consider geneticmay be due to AEDs causing a decrease in vitamin K– counselingdependent clotting factors and/or inhibiting placental Begin folate supplementation (4 mg/day)transport of vitamin K. Although a recent study of204 neonates born to mothers taking AEDs who did not During pregnancyreceive vitamin K supplementation showed no evidence Do not switch to an alternate AED solely to reduce terato-of coagulopathy,54 the general practice is to administer genic riskoral vitamin K (10 mg/day) during the last month of Check total and free levels of AEDs monthly (many AEDspregnancy and to administer 1 mg of vitamin K to the will require significant increases during pregnancy)infant at birth. Consider early genetic counselingSEIZURE RISK IN CHILDREN Check maternal serum AFP levels at 16 weeks’ gestation Children born to mothers with epilepsy have a great- Perform a level II fetal survey and ultrasonography ater risk of developing a seizure disorder. In 1 study of 687 18–20 weeks’ gestationchildren of parents with epilepsy, the cumulative in- Consider amniocentesis for AFP and acetylcholinesterasecidence of unprovoked seizures up to age 25 years was Administer vitamin K during the last month of pregnancyabout fourfold higher in the offspring of affected moth- Postpartumers than in the offspring of affected fathers (9% versus2%).55 However, maternal seizures during pregnancy do Encourage breastfeeding but counsel about avoiding sleep deprivationnot lead to an increased risk of epilepsy in the offspring. Continue to monitor AED blood concentrations closely;BREASTFEEDING anticipate adjustments over the next several months Breastfeeding while taking AEDs is generally encour- Counsel about extra safety tips for infant care as appropriateaged and safe in term infants and is endorsed by the (eg, changing clothing and diapers on the floor)American Academy of Neurology and the American Monitor for development of postpartum depressionAcademy of Pediatrics. The infant has already been AED = antiepileptic drug; AFP = α-fetoprotein. (Adapted with per-exposed to the AED for 9 months in utero. There is an mission from Delgado-Escueta AV, Janz, D. Consensus guidelines: pre-increased risk of infant sedation in women taking phe- conception counseling, management, and care of the pregnant womannobarbital or primidone. Infant serum levels may be with epilepsy. Neurology 1992;45:149.)helpful for monitoring toxicity. phenytoin with him. For several days after his return, heACUTE MENTAL STATUS CHANGE IN A PATIENT has been occasionally confused and complaining of aWITH EPILEPSY headache. This morning, after trying unsuccessfully to wake her husband, she witnessed a 2-minute convul- sion. The patient’s examination is significant for beingCASE 4 PRESENTATION stuporous but is otherwise unremarkable. A 40-year-old man with a history of focal epilepsy is • What is the differential diagnosis for a change inbrought by ambulance to the ED. The man is uncon- mental status in a patient with epilepsy?scious and is accompanied by his wife, who notes achange in mental status in her husband over the past A change in mental status is one of the most commonfew days culminating this morning in the inability to reasons for neurologic consultation, and the differentialwake up. The wife reports that her husband recently diagnosis is extensive. In the patient with epilepsy, spe-went on a 3-day camping trip and forgot to take his cial attention should be paid to medication toxicity,www.turner - white.com Neurology Volume 10, Part 1 11
  • Clinical Case Studies in Epilepsydrug-induced metabolic abnormalities, and the possi- known seizure disorder or other illnesses, trauma, focalbility of status epilepticus including nonconvulsive status neurologic signs, and signs of medical illness (eg, infec-epilepticus. There may be a common pathophysiology tion, substance abuse). After a convulsion has ended,of the change in mental status and epilepsy, such as in the patient should be carefully assessed for the possibil-cases of progressive epilepsies, mitochondrial disorders, ity of nonconvulsive or subtle ongoing seizures.and porphyria. Benzodiazepines are used as first-line agents in the acute management of seizures but are generally followedCASE CONTINUED in quick succession by a longer acting AED, most com- While evaluating the patient, his eyes and head devi- monly phenytoin. Lorazepam is the preferred benzodi-ate to the left. He then experiences a tonic-clonic sei- azepine due to a longer duration of antiseizure action.zure that lasts 5 minutes. Phenytoin (or fosphenytoin) is administered immediate- ly following lorazepam. If the patient is already taking• How is status epilepticus defined clinically? phenytoin, a dose of at least 10 mg/kg can be given while• What are the steps in management of patients with awaiting the serum level. status epilepticus? Further Work-upSTATUS EPILEPTICUS Once the patient is stabilized, a further diagnostic The most frequently used definition of status epilep- work-up may include head CT, lumbar puncture (LP),ticus, from the Epilepsy Foundation of America, is EEG, and brain MRI. Immediate EEG assessment is30 minutes of either continuous seizure activity or re- required if there is use of a long-acting paralytic agent,petitive seizures without recovery between them.56 This when there is no improvement or return to baselinedefinition was based on animal studies that have shown mental status after controlling overt convulsive move-neuronal death after 30 minutes of seizure activity, with ments, when the diagnosis is in doubt, or in cases of re-recovery seen in shorter time periods. The working def- fractory status epilepticus. In a prospective study, 164 pa-inition has been broadened by some to 2 seizures over tients who presented with convulsive status epilepticusany interval with no interval recovery or 1 seizure lasting were monitored by EEG for 24 hours following control5 minutes or longer.57 Most seizures last less than 2 min- of the presenting status epilepticus; 49% of the patientsutes58; therefore, any seizure lasting 5 minutes or longer continued to have seizures, and in 14%, there were nois of greater severity. DeLorenzo et al59 studied several clinical signs of the seizure activity.64hundred cases of prolonged seizures and found thatmore than half of all seizures lasting 10 to 29 minutes CASE CONTINUEDeventually required treatment for status epilepticus. The patient is given IV lorazepam, and IV phenytoin Estimates of the incidence of status epilepticus in the is started. The patient’s phenytoin level returns atUnited States range from 20 to 57 per 100,000 (higher 2 µg/mL, and he is given the full 20 mg/kg loadingincidence in non-whites) or about 150,000 cases each dose of phenytoin. His head CT and LP are normal. Noyear.60–62 In adults, about 22% of cases are related to AED further seizure activity is observed and his vital signs sta-withdrawal or insufficient AED levels.63 Alcohol with- bilize. However, the patient does not regain conscious-drawal, stroke, and anoxia are also common causes. ness and 30 minutes later has a second generalizedOther etiologies to consider include toxic-metabolic seizure lasting 5 minutes.conditions, CNS infections, tumor, and trauma. • How should this patient be treated at this point?Initial Management The initial management of the patient with status Management of Persistent Seizuresepilepticus consists of assessing the airway, assessing and An additional phenytoin bolus of 10 mg/kg can bemonitoring cardiorespiratory status, providing oxygen administered if seizures continue. Phenytoin is associat-and suctioning, obtaining intravenous (IV) access, ad- ed with the risk of hypotension and bradycardia. Theseministering an AED, and sending blood for laboratory side effects are less frequently seen with fosphenytoin,tests (Figure 3). Thiamine and glucose are adminis- but the increased cost of fosphenytoin limits its avail-tered unless the patient has a documented normal glu- ability. Other agents that may be used instead of pheny-cose level. A focused history from any available family toin or may follow phenytoin infusion if seizures contin-members, friends, or witnesses to the events and a neu- ue include IV valproate or phenobarbital. Phenobarbitalrologic examination are performed to assess for a is also associated with a risk of hypotension.12 Hospital Physician Board Review Manual www.turner - white.com
  • Clinical Case Studies in Epilepsy Status epilepticus Partial Generalized Simple Complex partial Convulsive Nonconvulsive (absence) Tonic-clonic Myoclonic Benzodiazepine Benzodiazepine Other AEDs Valproate Clonazepam Ethosuximide Valproate 0–5 min Assess airway and respiratory status; administer O2 Cardiac and blood pressure assessment/monitoring Establish IV access Send blood for CBC, electrolytes, renal function, glucose, magnesium, calcium, LFTs, ABG, AED levels, toxicology screen Administer thiamine 100 mg and 50 mL of 50% glucose (unless documented normo- glycemia) Focused history and neurologic examination 0–10 min (do not wait for AED levels to return) Lorazepam 2 mg (may repeat up to 0.1 mg/kg) at 2 mg/min Valproate Phenytoin Phenobarbital 20 mg/kg (200 mg/min) 20 mg/kg (< 50 mg/min) 15 mg/kg (100 mg/min) (or fosphenytoin 20 mg PE/kg [150 mg PE/min]) If no effect, reload 10 mg/kg CT, LP, MRI, EEG Refractory SE ICU, intubation, EEG monitoring < 60 min Propofol Pentobarbital Midazolam Bolus 1–3 mg/kg Bolus 5–20 mg/kg Bolus 0.15–0.2 mg/kg Infusion at 2–10 mg/kg/h Infusion at 0.5–3 mg/kg/h Infusion at 0.02–0.5 mg/kg/h Severe refractory SE Ketamine, lidocaine, thiopental, isofluorane (other AEDs via NGT)Figure 3. Algorithm for the treatment of status epilepticus (SE). AED = antiseizure drug; ABG = arterial blood gas analysis; CBC =complete blood count; CT = computed tomography; EEG = electroencephalogram; LFTs = liver function tests; LP = lumbar puncture;MRI = magnetic resonance imaging; NGT = nasogastric tube.www.turner - white.com Neurology Volume 10, Part 1 13
  • Clinical Case Studies in Epilepsy If seizures persist despite benzodiazepines and a sec- acidosis usually spontaneously corrects and does notond AED, status epilepticus is considered refractory and require use of sodium bicarbonate. Fever occurs in 28%will likely require drug-induced coma with intubation to 79% of patients and, based on evidence from the(if not already performed), intensive care unit admis- stroke literature, may be associated with a worse prog-sion, and continuous EEG monitoring. The medication nosis for neurologic recovery because it increases cere-is titrated to a burst-suppression pattern on EEG or sup- bral demand. Therefore, fever should be treated ag-pression of epileptiform activity. Medication-induced gressively. Transient leukocytosis also may occur. Withhypotension is to be expected and can be treated by prolonged seizures, a mild elevation in cerebrospinalslowing or stopping the infusion, giving fluid boluses, fluid white blood cells may be seen, although other eti-and using vasopressors as necessary. Historically, pento- ologies should be considered as well. Muscle creatinebarbital has been the agent most widely used. More phosphokinase is released and can lead to rhabdomyo-recently, midazolam and propofol have been used with lysis. Neurologic complications include cerebral edema,success. All these agents are thought to exert their anti- worsening of epilepsy, and residual cognitive and neu-seizure action by increased GABA-ergic activity. rologic deficits. If the patient fails to respond to these treatments, the Mortality rates range from 3% to 50% and are relatedstatus epilepticus is considered severely refractory and to the underlying condition,66 with status epilepticus duecarries with it an even higher risk of mortality. Further to anoxia having the highest mortality. Mortality is highesttreatment options include ketamine, lidocaine, thio- in the elderly. Other factors influencing mortality risk maypental, and isoflurane. Other AEDs, such as topiramate include level of consciousness at presentation, seizureand levetiracetam, can be administered via a nasogastric duration, and whether status epilepticus is refractory.tube and have been successful in some cases.• What physiologic changes occur in convulsive status CONCLUSION epilepticus? Initially there is a compensation phase. Cerebral Seizures and epilepsy are heterogeneous phenomenametabolism is greatly increased because of seizure activ- with varied etiologies, clinical courses, and outcomes,ity, but physiologic mechanisms are sufficient to meet but the unifying principle is the presence of corticalthe metabolic demands, and cerebral tissue is protected injury and/or dysfunction. The cases discussed involvefrom hypoxia or metabolic damage. Catecholamines common issues facing a neurologist. Once epilepsy hasare released, there is tachycardia, hypertension, in- been diagnosed, a thorough assessment for an underly-creased cardiac output, increased blood glucose, and ing cause should follow and include a detailed historyincreased cerebral blood flow as the body attempts to and physical examination, laboratory testing, neuroim-meet the increased oxygen and perfusion require- aging, and an EEG. The classification of epilepsy as wellments. After about 30 minutes, decompensation and as any medical comorbidities will guide selection of thehomeostatic failure begin. Cerebral blood flow, brain appropriate AED. Status epilepticus is a neurologicglucose, and oxygenation all decrease as the seizure emergency. It is important to consider nonconvulsivegoes on, the system can no longer keep up, and there is status epilepticus in patients whose mental status is nota decompensation phase. At this point, blood pressure recovering appropriately following a seizure and in hos-falls, cerebral blood flow does not keep up with de- pitalized patients with unexplained coma or change inmand, and neuronal damage occurs. mental status. Use of AEDs in status epilepticus is guid- ed by a protocol. Overall, a neurologist can have a mean-• What are the medical complications and mortality risk ingful impact on the medical care and quality of life of of convulsive status epilepticus? individuals with epilepsy at a variety of life stages.COMPLICATIONS AND MORTALITY RISK The medical complications of convulsive status epi- REFERENCESlepticus include neurologic, cardiac, respiratory, auto-nomic, and metabolic derangements and damage.65 1. Hauser WA, Annegers JF, Kurland LT. Incidence of epi-Many patients have a profound acidosis (with an arteri- lepsy and unprovoked seizures in Rochester, Minnesota:al pH < 7) that rapidly reverses with control of seizures. 1935–1984. Epilepsia 1993;34:453–68.The acidosis is generally metabolic due to increased lac- 2. Prognosis of epilepsy in newly referred patients: a multi-tate, but respiratory acidosis can be seen as well. The center prospective study of the effects of monotherapy on14 Hospital Physician Board Review Manual www.turner - white.com
  • Clinical Case Studies in Epilepsy the long-term course of epilepsy. Collaborative Group for 19. Hart RG, Easton JD. Seizure recurrence after a first, un- the Study of Epilepsy. Epilepsia 1992;33:45–51. provoked seizure. Arch Neurol 1986;43:1289–903. Annegers JF, Hauser WA, Elveback LR. Remission of sei- 20. Hauser WA, Anderson VE, Loewenson RB, McRoberts zures and relapse in patients with epilepsy. Epilepsia SM. Seizure recurrence after a first unprovoked seizure. 1979;20:729–37. N Engl J Med 1982;307:522–8.4. Cockerell OC, Johnson AL, Sander JW, et al. Prognosis of 21. Shinnar S, Berg AT, Moshe SL et al. The risk of recur- epilepsy: a review and further analysis of the first nine rence following a first unprovoked seizure in childhood: years of the British National General Practice Study of a prospective study. Pediatrics1990;85:1076–85. Epilepsy, a prospective population-based study. Epilepsia 22. Boulloche I, Leloup P, Mallet E et al. Risk of recurrence 1997;38:31–46. after a single unprovoked seizure. Dev Med Child Neurol5. MacDonald BK, Johnson AL, Goodridge DM, et al. Fac- 1989;31:626–32. tors predicting prognosis of epilepsy after presentation 23. Camfield PR, Camfield CS, Dooley JM et al. Epilepsy with seizures. Ann Neurol 2000;48:833–41. after a first unprovoked seizure in childhood. Neurology6. Proposal for revised clinical and electroencephalographic 1985;35:1657–60. classification of epileptic seizures. From the Commission 24. Das DP, Sawhney IM, Lal V et al. Risk of recurrence of on Classification and Terminology of the International seizures following single unprovoked idiopathic seizure. League Against Epilepsy. Epilepsia 1981;22:489–501. Neurol India 2000;48:35–60.7. Proposal for revised classification of epilepsies and epileptic 25. Browne TR, Holmes GL. Epilepsy [published erratum syndromes. Commission on Classification and Terminol- appears in N Engl J Med 2001;344:1956]. N Engl J Med ogy of the International League Against Epilepsy. Epilepsia 2001;344:1145–51. 1989;30:389–99. 26. Camfield PR, Camfield CS, Dooley JM, et al. Epilepsy8. Engel J Jr. A proposed diagnostic scheme for people with after a first unprovoked seizure in childhood. Neurology epileptic seizures and with epilepsy: report of the ILAE 1985;35:1657–60. Task Force on Classification and Terminology. Interna- 27. Gardiner M. Genetics of idiopathic generalized epilep- tional League Against Epilepsy (ILAE). Epilepsia 2001;42: sies. Epilepsia 2005;46 Suppl 9:15–20. 796–803. 28. Ramsay RE, Rowan AJ, Pryor FM. Special considerations9. Annegers JF, Rocca WA, Hauser WA. Causes of epilepsy: in treating the elderly patient with epilepsy. Neurology contributions of the Rochester epidemiology project. 2004;62(5 Suppl 2):S24–9. Mayo Clin Proc 1996;71:570–5. 29. Sander JW, Hart YM, Johnson AL, Shorvon SD. National10. Annegers JF, Hauser WA, Shirts SB, Kurland LT. Factors General Practice Study of Epilepsy: newly diagnosed epi- prognostic of unprovoked seizures after febrile convul- leptic seizures in a general population. Lancet 1990;336: sions. N Engl J Med 1987;316:493–8. 1267–71.11. Salazar AM, Jabbari B, Vance SC, et al. Epilepsy after pen- 30. Rowen AJ. Seizure. Fundamentals of drug management etrating head injury. I. Clinical correlates: a report of the of epilepsy in the older patient. Geriatrics 2002;57:33–8. Vietnam Head Injury Study. Neurology 1985;35:1406–14. 31. DeLorenzo RJ, Hauser WA, Towne AR, et al. A prospec-12. Annegers JF, Grabow JD, Groover RV, et al. Seizures after tive, population-based epidemiologic study of status head trauma: a population study. Neurology 1980;30 epilepticus in Richmond, Virginia. Neurology 1996;46: (7 Pt 1):683–9. 1029–35.13. Crawford PM, West CR, Chadwick DW, Shaw MD. Arter- 32. Lancman ME, Golimstok A, Norscini J, Granillo R. Risk iovenous malformations of the brain: natural history in factors for developing seizures after a stroke. Epilepsia unoperated patients. J Neurol Neurosurg Psychiatry 1993;34:141–3. 1986;49:1–10. 33. So EL, Annegers JF, Hauser WA, et al. Population-based14. Casazza M, Broggi G, Franzini A, et al. Supratentorial cav- study of seizure disorders after cerebral infarction. Neur- ernous angiomas and epileptic seizures: preoperative ology 1996;46:350–5. course and postoperative outcome. Neurosurgery 1996; 34. Cleary P, Shorvon S, Tallis R. Late-onset seizures as a pre- 39:26–32. dictor of subsequent stroke. Lancet 2004;363:1184–6.15. Annegers JF, Hauser WA, Beghi E, et al. The risk of un- 35. Drury I, Beydoun A. Interictal epileptiform activity in provoked seizures after encephalitis and meningitis. elderly patients with epilepsy. Electroencephalogr Clin Neurology 1988;38:1407–10. Neurophysiol 1998;106:369–73.16. Kinnunen E, Wikstrom J. Prevalence and prognosis of 36. Drury I, Selwa LM, Schuh LA, et al. Value of inpatient epilepsy in patients with multiple sclerosis. Epilepsia diagnostic CCTV-EEG monitoring in the elderly. Epilep- 1986;27:729–33. sia 1999;40:1100–2.17. Nelson KB, Ellenberg JH. Antecedents of seizure disorders 37. Prior FM, Ramsay RE, Rowan AJ, et al. Utility of extend- in early childhood. Am J Dis Child 1986;140:1053–61. ed EEG recordings in the diagnosis of epilepsy in the18. Ottman R, Annegers JF, Hauser WA, Kurland LT. Seizure elderly [abstract]. Epilepsia 2001;42 Suppl 7:27. risk in offspring of parents with generalized versus partial 38. McBride AE, Shih TT, Hirsch LJ. Video-EEG monitoring epilepsy. Epilepsia 1989;30:157–61. in the elderly: a review of 94 patients. Epilepsia 2002;43:www.turner - white.com Neurology Volume 10, Part 1 15
  • Clinical Case Studies in Epilepsy 165–9. function in women with epilepsy: recommendations for39. Greenberg MK, Barsan WG, Starkman S. Neuroimaging evaluation and management. J Neurol Neurosurg Psychi- in the emergency patient presenting with seizure. Neur- atry 2002;73:121–5. ology 1996;47:26–32. 53. Wallace H, Shorvon S, Tallis R. Age-specific incidence40. Lackner TE, Cloyd JC, Thomas LW, Leppik IE. Antiepi- and prevalence rates of treated epilepsy in an unselected leptic drug use in nursing home residents: effect of age, population of 2,052,922 and age-specific fertility rates of gender, and comedication on patterns of use. Epilepsia women with epilepsy. Lancet 1998;352:1970–3. 1998;39:1083–7. 54. Choulika S, Grabowski E, Holmes LB. Is antenatal vita-41. Leppik IE. Choosing an antiepileptic: selecting drugs for min K prophylaxis needed for pregnant women taking old patients with epilepsy. Geriatrics 2005;60:42–7. anticonvulsants? Am J Obstet Gynecol 2004;190:882–3.42. Teramo K, Hiilesmaa V, Bardy A, Saarikoski S. Fetal heart 55. Ottman R, Annegers JF, Hauser WA, Kurland LT. Higher rate during a maternal grand mal epileptic seizure. risk of seizures in offspring of mothers than of fathers J Perinat Med 1979;7:3–6. with epilepsy. Am J Hum Genet 1988;43:257–64.43. Kaaja E, Kaaja R, Hiilesmaa V. Major malformations in off- 56. Treatment of convulsive status epilepticus. Recommenda- spring of women with epilepsy. Neurology 2003;60:575–9. tions of the Epilepsy Foundation of America’s Working44. Artama M, Auvinen A, Raudaskoski T, et al. Antiepileptic Group on Status Epilepticus. JAMA 1993;270:854–9. drug use of women with epilepsy and congenital malfor- 57. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl mations in offspring. Neurology 2005;64:1874–8. J Med 1998;338:970–6.45. Wide K, Winbladh B, Kallen B. Major malformations in 58. Theodore WH, Porte RJ, Albert P, et al. The secondarily infants exposed to antiepileptic drugs in utero, with em- generalized tonic-clonic seizure: a videotape analysis. phasis on carbamazepine and valproic acid: a nation- Neurology 1994;44:1403–7. wide, population-based register study. Acta Paediatr 2004; 59. DeLorenzo RJ, Garnett LK, Towne AR, et al. Comparison 93:174–6. of status epilepticus with prolonged seizure episodes last-46. Holmes LB, Wyszynski DF, Lieberman E. The AED (anti- ing from 10 to 29 minutes. Epilepsia 1999;40:164–9. epileptic drug) pregnancy registry: a 6-year experience. 60. DeLorenzo RJ, Hauser WA, Towne AR, et al. A prospec- Arch Neurol 2004;61:673–8. tive, population-based epidemiologic study of status47. Vinten J, Adab N, Kini U, et al. Neuropsychological effects epilepticus in Richmond, Virginia. Neurology 1996;46: of exposure to anticonvulsant medication in utero. Liver- 1029–35. pool and Manchester Neurodevelopment Study Group. 61. Hesdorffer DC, Logroscino G, Cascino G, et al. Incidence Neurology 2005;64:949–54. of status epilepticus in Rochester, Minnesota, 1965–1984.48. Reinish JM, Sanders SA, Mortensen EL, Rubin DB. In Neurology 1998;50:735–41. utero exposure to phenobarbital and intelligence deficits 62. Logroscino G, Hesdorffer DC, Cascino G, et al. Time in adult men. JAMA 1995;274:1518–25. trends in incidence, mortality, and case-fatality after first49. Cunnington M, Tennis P. Lamotrigine and the risk of episode of status epilepticus. Epilepsia 2001;42:1031–5. malformations in pregnancy International Lamotrigine 63. Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determi- Pregnancy Registry Scientific Advisory Committee. Neur- nants of mortality in status epilepticus. Epilepsia 1994;35: ology 2005;64:955–60. 27–34.50. Hauser WA, Rich SS, Lee JR, et al. Risk of recurrent 64. DeLorenzo RJ, Waterhouse EJ, Towne AR, et al. Persistent seizures after two unprovoked seizures. N Engl J Med nonconvulsive status epilepticus after the control of con- 1998;338:429–34. vulsive status epilepticus. Epilepsia 1998;39:833–40.51. A randomized controlled trial of chronic vagus nerve 65. Shorvon S The management of status epilepticus. J Neurol stimulation for treatment of medically intractable sei- Neurosurg Psychiatry 2001;70 Suppl 2:II22–7. zures. The Vagus Nerve Stimulation Study Group. Neur- 66. Rossetti AO, Logroscino G, Bromfield EB. Refractory sta- ology 1995;45:224–30. tus epilepticus: effect of treatment aggressiveness on prog-52. Bauer J, Isojarvi JI, Herzog AG, et al. Reproductive dys- nosis. Arch Neurol 2005;62:1698–702. Copyright 2006 by Turner White Communications Inc., Wayne, PA. All rights reserved.16 Hospital Physician Board Review Manual www.turner - white.com